Acute Myeloid Leukemia

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ARCHIVES OF HELLENIC MEDICINE: ISSN 11-05-3992
ABSTRACTS
ARCHIVES OF HELLENIC MEDICINE 2015, 32(Suppl 1):17-49
fcecdedefed-49
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tion. Combining verapamil with other chemotherapeutic drugs

ACUTE MYELOID LEUKEMIA may result in increasing effect in AML treatment.
P01
EFFECT OF THE CALCIUM CHANNEL BLOCKER
P02
VERAPAMIL ON CELL CYCLE AND APOPTOSIS IN AML ACUTE MYELOID LEUKEMIA RELAPSING AS
CANCER CELL LINES (HL-60) GRANULOCYTIC SARCOMA OF THE UTERINA CERVIX:
Gulper NACARKAHYA1, Mehmet YLMAZ2, A CASE REPORT
Ibrahim Halil KILIC3, Isik Didem KARAGOZ3, Muhammet MADEN1, Gulsum Emel PAMUK1,
Ebru TEMZ1, Mehmet OZASLAN3 Demet TEKATAS2, Mehmet Sevki UYANK1
1
Gaziantep University School of Medicine, Department 1
Department of Hematology, Trakya University, Edirne,
of Medical Biology, Gaziantep, Turkey, 2Gaziantep Turkey, 2Department of Internal Medicine, Edirne State
University School of Medicine, Department of Hematology, Hospital, Edirne, Turkey
Gaziantep, Turkey, 3Gaziantep University School of
Medicine, Department of Molecular Biology, Gaziantep, Introduction: Granulocytic sarcoma (GS) is defined as a tumor
Turkey mass composed of immature myeloid cells localized in any
extramedullary site. GS can be isolated or encountered during
Objective: The drugs that are used in the chemotherapeutic the course of acute myeloid leukemia (AML), myelodysplastic
treatment of cancer are quite toxic effects on target cells. To this syndrome or chronic myeloproliferative neoplasms. It may be
end, giving specific doses of verapamil to the HL-60 AML cell line detected coexistent with the initial diagnosis of these diseases
and apoptosis and cell cycle was evaluated. or may be seen in the relapse or as the first sign of the disease
Methods: HL-60 AML cell line was selected in this study. This cell relapse. We present the case of a patient whose disease relapsed
line containing 10% FCS with 1% penicillin and streptomycin as GS of the uterine cervix.
produced sub cultured in RPMI-1640. The effective dose (viability Case: A 63-year-old female AML diagnosed patient who was
value) was determined by MTT method by 10, 30, 50, 80 M of given radiotherapy for 2 days after the cervix uteri cancer pre-
giving increasing doses verapamil to the HL-60 cell line 24 hours diagnosis, followed for 1,5 years in remission, applied to hema-
incubation. Determined the effective dose of verapamil, given to tology department with complain of dysuria. In the blood count
HL-60 cells, cycle and apoptosis were examined by flow cytometry. leukocyte 61400/uL, hemoglobin 10.2 g/dL, platelets 24000/Ul, in
In Saline with HL-60 cells were used as control. the biochemical analysis, urea 150 mg/dl, creatinine 2.5 mg/dL,
Results: Verapamil (50 M) lead to increased programmed cell LDH 1179 U/L, and in the peripheral blood smear, 60% myeloid
death ratio at the 24.hours compared to control and this result and monostoid blasts were detected. In the all abdominal MRI,
was statistically significant (p <0.05). Diploid cell cycle verapamil a rectum and bladder invasive mass which infiltrated the cervix
untreated group in G1 phase decreased according to verapamil uteri completely were detected. Endocervical curettage biopsy
treated group and a significant increase in S phase formed a (MPO and CD117 positive, CD34, TDT, Ki67, HPV, p53 negative) was
significant difference (p <0.05), but formed no significant dif- compatible with GS and in the bone marrow biopsy 95% blasts
ference (p >0.05) in G2 phase. When the ratio of aneuploid cells was detected and the patient was diagnosed with relapse AML
in the G1 phase of verapamil untreated group compared to the accompanied by GS. Idarubicin+Ara-C induction chemotherapy
group administered with verapamil creates increased a significant was initiated and the patient died of sepsis on the 24th day of
difference (p <0.05). Decrease in S phase does not constitute a chemotherapy.
significant difference (p >0.05). Conclusion: Clinically the incidence of GS in AML is 35%.The
Conclusion: The first main control point is DNA damage censor presence of GS is associated with a generally poor outcome and
in the transition of G1/S phase. In the early to mid-G1 phase of a shorter overall survival. GS can be found in almost any organ:
damaged cells in the G1 phase are hanged back, damaged cells in the most common sites of involvement are bones, soft tissues,
late G1 phase, will continue in the S phase. Thus, cell G1/S transi- lymph nodes, skin, gastrointestinal tract. GS of the uterine cervix
tion of the cell phase ratios we have achieved with verapamil is is very rare. MPO is the single most sensitive and specific antibody
arrested synchronization, which is consistent with this informa- for detection of myeloid differentiation.
18 2nd AGEAN HEMATOLOGY ONCOLOGY SYMPOSIUM, Abstracts
P03 dose all trans retinoic acide (ATRA) and arsenic trioxide (ATO)
because of bilateral sixth nerve palsies possibly associated with
A CASE REPORT: GRANULOCYTIC SARCOMA WHICH arsenic trioxide achieving molecular complete remission.
CAN BE CONFUSED WITH HISTIOCYTIC SARCOMA Case: A 30-year-old female patient was admitted to our depart-
Ali GOKYER1, Mehmet Sevki UYANIK2, ment in November 2014. Pancytopenia was identified in this
Gulsum Emel PAMUK2 patient. Bone marrow aspiration biopsy was reported as acute
1
Trakya University, Department of Internal Medicine, myeloid leukemia. RT-PCR showed the proportion of fusion gene
Trakya, Turkey, 2Trakya University, Department of PML-RAR was positive (53%). Diagnosis of APL was confirmed
Hematology, Trakya, Turkey and treatment was started. She developed sudden blurred vision
and diplopia. She developed an isolated bilateral 6th nerve palsies,
Introduction: Granulocytic sarcoma is a solid tumor formed by more prominent on the left side, which were at onset suspected
granulocyte precursors outside of bone marrow. Granulocytic to be caused by isolated leukemic infiltration. The cerebrospinal
sarcoma may manifest as a sign of acute myeloid leukemia (AML). fluid examination and brain MRI were performed in terms of
In this case report, the patient we aimed to present was firstly nerve involvement and resulted normal. So 6th nerve palsies
diagnosed with histiocytic sarcoma after undergoing a biopsy, were considered to be caused by a drug reaction. ATRA and ATO
later he underwent a lymph node biopsy from the neck area to treatment was stopped and she was followed. Her complaints
confirm this diagnosis, which resulted in granulocytic sarcoma. improved. She was treated with ATRA at 40mg/day for 15 days
Case: A 58-year-old male patient who was diagnosed of histiocytic and idarubicin at 5mg/m2 for 4 days per week. Consolidation
sarcoma after tonsillectomy. The patient consulted us. Blood count treatment with ATRA has been continued seamlessly therefore
results were as follows: leukocyte 7330/uL, hemoglobin 14.5 gr/ adverse ocular reaction was considered to be possibly associated
dl, thrombocyte 314000/uL. Biochemical analysis resulted was with arsenic trioxide.
normal. Peripheral blood smear test did not reveal any atypical Conclusion: Treatment with ATO is alarming to patients and physi-
cells, however during bone marrow biopsy 3-4% immature cells cians alike due to the broad adverse effect profile. Unexplained
were detected. In the PET-CT, lymph node located in the left- strabismus and diplopia should be evaluated as a potential
cervical section was considered. After excision, positive staining sign of CNS involvement and initially conventional imaging
with myeloperoxidase (MPO), CD68, CD34 and CD56 markers and cerebrospinal fluid examination should be performed. If
confirmed the diagnosis of granulocytic sarcoma. The patient CNS involvement of APL is not detected, abducens nerve palsy
was administered idarubicin + cytosine arabinoside protocol. can be considered to be caused by a drug reaction. Herewith a
Upon detecting a progression in the following thoracic CT scan thorough understanding of the safety and potential side effects
the patient was administered high dose cytosine arabinoside of ATO as a therapeutic agent is necessary, in order to minimize
+ idarubicin protocol. The mass regressed. However, after this its toxic complications.
therapy the patient died from opportunistic fungal infection.
Conclusion: Granulocytic sarcoma may occur in relation with
AML. It is involved with central nervous system, skin and lymph P05
nodes. It is a sign of poor prognosis for 2-14% of patients suffer-
CLINICAL ANALYSIS OF 11 PATIENTS WITH MYELOID
ing from AML. Very occasionally it does not accompany AML, in
SARCOMA AS A SINGLE CENTER EXPRIENCE
our case bone marrow biopsy resulted with a myeloblast ratio
of 4% and thus AML was not present. In our case, during cervical
Mehmet YILMAZ, Hamit YILDIZ, Erdal GUNDOGAN,
LAM biopsy MPO, CD68, CD34 and CD56 markers were confirmed
Mustafa PEHLVAN, Vahap OKAN, Ibrahim SARI
and thus the patient was diagnosed with granulocytic sarcoma. Gaziantep University, Department of Hematology,
Gaziantep, Turkey
P04 Objective: Myeloid sarcoma (MS) represents the proliferation

and accumulation of myeloblasts at extramedullary sites. While
BILATERAL SIXTH NERVE PALSIES POSSIBLY extramedullary involvement in acute myeloblastic leukemia (AML)
ASSOCIATED WITH ARSENIC TRIOXIDE IN ACUTE is uncommon in itself, MS without any bone marrow involvement
PROMYELOCYTIC LEUKEMIA are extremely rare and has a diagnostic and therapeutic challenge.
Pusem PATIR1, Merve Guner OYTUN2, Anl OZLUK2, Here, we presented the clinical features, diagnosis, treatment
Alide ALIYEVA2, Ayhan DONMEZ1, Murat TOMBULOGLU1 modality and results of MS patients as a single center experience.
1
Ege University Faculty of Medicine, Department of Methods: This study included evaluation of 11 patients with MS
Hematology, Izmir, Turkey, 2Ege University Faculty of from March 2010 to January 2014, retrospectively.
Medicine, Department of Internal Medicine, Izmir, Turkey Results: Seven of 11 patients were male 4 were female. Median
age was 41.0. The patients were presented with the involvement of
Introduction: Herein, we reported an 30-year-old patient with L3-SI vertebra (1), conjunctiva (1), eye lid (1), lower cervical region
acute promyelocytic leukemia (APL) who was treated with low- (1), skin (1), testis (1), inguinal region (2), and pharynx (3). Chronic
ARCHIVES OF HELLENIC MEDICINE 32(Suppl 1), 2015 19
myeloid leukemia was developed after MS was diagnosed and 2 sorting of CD34+ cells of patients samples, while mononuclear
months later accelerated to blastic phase in 1 of 11 patients. He blood cells from healthy individuals were used as controls.
was treated with combined chemotherapy regimens, after achiev- Small RNA (<200 b) was isolated using the NucleoSpin miRNA
ing complete remission HLA identical unrelated bone marrow kit (Macherey Nagel). Simultaneous quantification of 84 apop-
transplantation (BMT) was performed. But He was died related tosis- associated miRNAs was performed by using the miScript
to chronic graft versus host disease and pulmonary aspergillosis miRNA PCR Array Human Apoptosis (MIHS-114ZF, Qiagen) in a
6 months later after BMT. Among 11 patients 6 were treated with LightCycler 480 instrument (Roche AG, Rotkreuz, Switzerland),
chemotherapy, 2 chemotherapy plus radiotherapy, 5 patients and relative quantitation of expression was determined by the
were treated without chemotherapy, but treated with surgical comparative CT method. For miRNA target prediction we used
resection. Of 3 of 11 patients were follow out after diagnosis of the RNA22 tool: http://cm.jefferson.edu/rna22v2 and http://
MS. Chemotherapy regimen was combined with idarubicine cm.jefferson.edu/rna22v2.0.
and cytarabine similar to AML. The average survival time of MS Results: We found 51 downregulated and 12 upregulated miRNAs
patients treated with or without chemotherapy were 19 and 11 compared to control. Among the downregulated miRNAs was
months respectively, suggesting prolonging of survival time of the miR-29 family and among the upregulated was the miR-181
patients treated with chemotherapy. The average survival time family, both of which have been previously implicated in AML.
of MS patients treated with chemotherapy plus radiotherapy The top 10 downregulated miRNAs were miR-31-5p, miR-451a,
was 23 months, better than chemotherapy alone and without miR-144-3p, miR-29b-3p, miR-204-5p, miR-9-5p, miR-409-3p,
chemotherapy. Moreover one patient who was treated using miR- 542-3p, miR-29c-3p and miR-29a-3p, whereas the top 10
chemotherapy combined with BMT is not alive now, living times upregulated miRNAs were miR-186-3p, miR-149-3p, let-7c-5p,
was 26 months. miR-222- 3p, miR-214-3p, miR-181c-5p, miR-181a-5p, miR-181b-
Conclusion: We found that chemotherapy similar as treatment 5p, miR-34a-5p and miR-181d-5p. Deepest downregulation (over
of AML can decrease the probability of disease progressing into -50fold) was seen for miR-144-3p, miR-451a and miR-31-5p. We
bone marrow abnormality, and if chemotherapy combines with used RNA22 to identify genes that are predicted to be simultane-
radiotherapy and bone marrow transplantation, the survival ously targeted by all of the 10 top downregulated miRNAs and
time of MS patients can be longer. More research is necessary also the genes that are predicted to be simultaneously targeted
to elucidate the molecular pathogenesis of MS, its prognostic by all of the 10 top upregulated miRNAs. The predicted targets
impact, and optimal treatment modalities. for all top 10 downregulated miRNAs include NSD1, KAT6B and
SACS. NSD1 is an histone methyltransferase, whereas KAT6B is
an histone acetyltransferase. The predicted targets of all top 10
P06 upregulated miRNAs include 36 genes among which are DICER1,
ZNF507, ZNF704 and MLLT6.
EXPRESSION PROFILING OF A PANEL OF APOPTOSIS-
Conclusion: A variety of microRNAs are dysregulated in patients
ASSOSSIATED MICRORNAS IN ACUTE MYELOID
with AML. We confirm that the miR-29 family and the miR-181
LEUKEMIA IDENTIFIES DIFFERENTIALLY EXPRESSED
family have altered expression in AML. Among predicted targets
MICRORNAS THAT TARGET EPIGENETIC MODIFIERS
of the downregulated miRNAs are genes involved in chromatin
Eleftheria HATZIMICHAEL1,2,Aggeliki DASOULA3, remodelling, suggesting that altered function of epigenetic
Maria IGGLEZOU3, Andreas KATSENOS3, Ioannis SAINIS3, modifiers in AML may be due to dysregulation of miRNAs.
Isidore RIGOUTSOS2, Evangelos BRIASOULIS1
1
Department of Hematology, University of Ioannina,
Ioannina, Greece, 2Computational Medicine Center, Sidney
Kimmel Medical College, Thomas Jefferson University,
Philadelphia, PA, U.S.A., 3Cancer Biobank Center, University
of Ioannina, Ioannina, Greece
Objective: Identifying molecular aberrations in Acute Myeloid

Leukemia (AML) is still an unmet research target. We evaluated
the expression of a panel of apoptosis-associated microRNAs
(miRNAs) in leukemic blasts isolated from AML patients and
investigated their predicted targets.
Methods: We used bone marrow or peripheral blood that were
donated by eight AML patients (5 male, 3 female) at diagnosis.
Mononuclear cells were isolated by Ficoll-Histopaque (Sigma
Aldrich) density gradient centrifugation and were cryopreserved
in liquid nitrogen at the Cancer Biobank Center of the University
of Ioannina. MicroBeads technology was used for magnetic cell
P08
MYELODYSPLASTIC SYNDROMES
HEREDITARY ICHTHYOSIS VULGARIS AND
& PAROXYSMAL NOCTURNAL MYELODYSPLASTIC SYNDROME: A CASE REPORT
HEMOGLOBINURIA Pelin AYTAN1, Kvlcm ERDOAN2, Emel GRKAN3
1
Mersin State Hospital, Department of Hematology,
P07 Mersin,Turkey, 2ukurova University Balcal Medical
RETROSPECTIVE EVALUATION OF DEMOGRAPHIC Hospital, Department of Pathology, Adana, Turkey,
AND CLINICAL FEATURES OF PATIENTS WITH MDS:
3
ukurova University Balcal Medical Hospital, Department
SINGLE CENTER EXPERIENCE of Hematology, Adana, Turkey
Glay ALP1,Mahmut TB2, Fahri AHN2, Introduction: Hereditary ichthyosis (HI) vulgaris is an autosomal
Murat TOMBULOLU2, Gray SAYDAM2 dominant disease first evident in early childhood. Unlike acquired
1
Ege University School of Medicine, Department of ichthyosis HI is rarely associated with hematologic malignancies.
Internal Medicine, Izmir, Turkey, 2Ege University School In this case we present a girl with HI vulgaris with MDS-RAEB.
of Medicine, Department of Hematology, Izmir, Turkey Case: G.A. is a twenty-one-year-old girl who has HI vulgaris. She
has been consultated by her dermatologist because of her anemia.
Objective: Myelodysplastic syndromes are heterogenous disease Otherwise she had no symptoms. She had hepatosplenomegaly
and have complex clinical presentation. Clinical and demographic and different types of scaling in different areas. There is moder-
data of 158 patients with Myelodysplastic Syndrome (MDS) ate ectropion where the exposed conjunctiva was thickened
followed in Ege University School of Medicine Department of and hyperaemic. The laboratory findings were: WBC:3.11 K/uL,
Hematology, were analyzed retrospectively. HGB:11.2 g/dl, NE:1.54K u/L, MCV:814 fL, PLT:89 Ku/L, AST:70 U/L,
Methods: Those patients who were followed-up with the diag- ALT:60 U/L, LDH:199 U/L. In her peripheral blood smear there
nosis of MDS, were evaluated in terms of their ages, genders, were anisocytosis, hyposegmentated and hypogranular neutro-
complaints and laboratory values based on their files. phils and low thrombocyte level. In her bone barrow aspiration
Results: The average age at the time of diagnosis was 66 years there were hypolobulated neutrophils, eryhtroid serial dysplasia,
old. While 79 of them were male, 79 cases were female. 27.2% dismegakaryopoesis and 6-8% elevated blasts. She is now using
(43) of the patients were in low risk MDS group, 48.7% (77) were topical retinoids that her dermatologist suggested. She has been
intermediate-1, 9.5% (15) were intermediate-2 and 4.4% (7) were following by the haematology clinic for about seven months. Her
patients with high risk MDS according to IPSS. 50% (79) of patients family and she went for HLA matching testing for probable future
had RA, 13.3% (21) had RAEB-2, 3.2% (5) had RARS, 8.9% (14) had allogeneic bone marrow transfusion. In her follow-ups there has
RAEB-1, 19,7% (31) RCMD, 3.8% (6) had RT and 5q syndrome and been no need for blood transfusion and her neutrophil level has
9.5% of patients had secondary MDS. Twenty-nine of the 114 pa- never been below 500 K/uL.
tients that were checked for cytogenetic analysis, had abnormal Conclusion: The myelodysplastic syndromes (MDS) compose a
cytogenetic. For the cytogenetic analysis; 12 patients had 5q heterogenous group of clonal stem cell disorders characterized
deletion, 9 patients had trisomy 8, 3 patients had 20 q deletion, by ineffective hematopoiesis in one or more cell lineages and
7 patients had 7 q deletion and 3 patients had RB1gen (13q14) have a propensity to progress to AML. MDS patients are often
mutations were observed. Median survival was calculated as 24 asymptomatic and the diagnosis is made at the time of routine
months. During the follow up period, 10 patients progressed to laboratory screening tests that reveal cytopenias in one or
AML. Twelve percent (19) of the 158 patients died during the more lines or dysplasia on the blood smear. There are not many
follow-up period. Disease progression and infections were the cases in literature that report an association between HI and
major causes of the death. 4 patients had progression AML and hematologic malignancies. In the present case the patient with
15 patients died because of the co-morbidities. HI also has MDS-RAEB which has a potential to progress acute
Conclusion: Myelodysplastic syndromes are complicated and myeloid leukemia.
heterogeneous disorders which are not well understood yet.
Individualized approach is essential for these patients. Clinical
and demographic characteristics of each patient should be
determined before therapy.
P09
CHRONIC LYMPHOCYTIC LEUKEMIA
THE AWARENESS OF PNH: A SINGLE CENTER
EXPERIENCE FROM ANTALYA, TURKEY & HAIRY CELL LEUKEMIA
Hatice DUMAN1, Ozan SALIM1,Orhan Kemal YUCEL1,
Melike ULUBAHSI1, Hediye SOLTEKIN1, Merve AYCICEK1,
P10
Erdal KURTOGLU2, Levent UNDAR1 ZAP-70 AND CD38 EXPRESSION AS A PROGNOSTIC
1
Department of Hematology, Akdeniz University, Antalya, MARKER FOR CHRONIC LYMPHOCYTIC LEUKEMIA
Turkey, 2Department of Hematology, Antalya Ataturk Ahmet Krad GNE, Mesude FALAY, Funda CERAN,
Research and Training Hospital, Antalya, Turkey Simten DADA, Glsm ZET
Ankara Numune Training and Research Hospital,
Objective: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare,
Department of Hematology, Ankara, Turkey
acquired, life-threatening but treatable disease characterized
mainly by destruction of red blood cells by the complement Objective: Chronic Lymphocytic Leukemia (CLL) is one of the
system. The heterogeneity of the clinical manifestations and most common type of leukemias and lymphioid malignancies
lack of awareness of PNH may cause delayed diagnosis. The in adults. In The last decade several studies revelaed some new
fluorescein-labeled proaerolysin (FLAER) test by using flow prognostic markers like IgVH mutational status, iFISH, ZAP-70, CD
cytometry is the gold standard methodology for screening of 38. IgVH gene analysis is time consuming, expensive and difficult.
paroxysmal nocturnal hemoglobinuria. ZAP-70 and CD38 expression is associated with IgVH mutation.
Methods: We analyzed 388 cases screened for PNH with FLAER The co-expression of these two molecules in neoplastic B cells
according to the main symptoms and laboratory findings from is associated with high risk disease.
2012 to 2015 in Akdeniz University Hospital, retrospectively. Methods: We aimed to assess the prognostic significance of cor-
Results: The median age was 47 years (range: 1-94 years) and relation between ZAP-70 and CD38 expression by the different
the M/F ratio was 178/210. The commonest reason for screening cut-off values of CD38. A total of 124 CLL patients referred to our
for PNH at onset were PNH related symptoms (30.7%) (weak- clinic were retrospectively analyzed.
ness, dyspnea, abdominal and chest pain, erectly dysfunction Results: The immunophenotype of all patient was CD5+CD19+
and dyspahegae), bone marrow failure syndromes (28.3%) and CD20+CD23+Ig light chain /. The CD 38 were analysed in
thrombosis (29.6%). Screening was performed in hematology CD5+CD19+ cells. ZAP-70 was assessed in CD19+ B cells. The
and internal medicine department, respectively. Positive FLAER cut-off value of ZAP-70 were 20%. By CD38 there are two cut-off
results were detected nearly 10 percent of patients (38/388, 9.8%). values, 7% and 20%. 124 patients, 85 male and 39 female ages
Conclusion: PNH should be considered as a differential diag- between 31-87. By RAI staging; 50 patient stage 0 (40.3%), 21
nosis in patients with unexplained abdominal pain, dyspnea, stage I (16.9%), 11 stage II (8.9%), 24 stage III (19.4%), 18 stage IV
renal failure, thrombosis and non-immune hemolytic anemia. (14.5%). Median follow up is 36 months (4-68 months). When the
Awareness of the possibility in a potential case is crucial for early 20% cut-off applied for CD38, 62 patients were CD38(-)/ZAP70(-),
diagnosis of PNH. 26 patients CD38(+)/ZAP70(+), 28 patients were in CD38/ZAP70
incompatible group. When the 7% cut-off value applied for CD38,
49 patients were CD38(-)/ZAP70(-), 48 patients CD38(+)/ZAP70(+)
and 27 patients were in CD38/ZAP70 incompatible group. In
the both cut off values for CD38, the double negative patients
(CD38-/ZAP70-) have a higher remission time than double positive
ones (CD38+/ZAP70+). 20% group: 58.83.3 months; 7% group:
66.45.8 months (p <0.001). When the incompatible groups
compared for both cut-off values the CD38-/ZAP70+ group had
a higher remission time than CD38+/ZAP70+ ones (20% group:
16.42.5 months, 7% group: 47.333.4 months).
Conclusion: Detection of CD38 and ZAP70 expression by flow
cytometry is easier and cheaper than IgVH mutation analysis.
In CLL patients co-expression of CD38/ZAP70 is associated with
poor prognosis and double negative group is related with a better
prognosis. When the incompatible group analyzed the CD38-/
ZAP70+ patients have a better prognos and higher treatment
free survival.
P11 that may benefit from anti-STAT agents and paves the way for a
more intensive study of the role of EBV in CLL.
PROGNOSTIC SIGNFICANCE OF SIGNAL
TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION
5 AND 5B EXPRESSION IN EPSTEIN-BARR VIRUS P12
POSITIVE PATIENTS WITH CHRONIC LYMPHOCYTIC
LEUKEMIA CLADRIBINE RELATED SEVERE AND FATAL BONE
MARROW APLASIA IN A PATIENT WITH HAIRY CELL
Panagiotis DIAMANTOPOULOS1,Maria SOFOTASIOU1,
LEUKEMIA
Zafeiroula GEORGOUSI2, Neefeli GIANNAKOPOULOU1,
Vasiliki PAPADOPOULOU1, Athanasios GALANOPOULOS3, Ozlem KARPUZ1,Ramazan ERDEM1, Utku ILTAR1,
Marie-Christine KYRTSONIS4, Aglaia DIMITRAKOPOULOU1, Orhan Kemal YUCEL1, Ozan SALIM1, Ozge TURHAN2,
Nikolaos SPANAKIS1, Nora-Athina VINIOU1 Bahar AKKAYA3, Levent UNDAR1
1
First Department of Internal Medicine, National and
1
Department of Hematology, Akdeniz University, Antalya,
Kapodistrian University of Athens, School of Medicine, Turkey, 2Department of Infectious Diseases and Clinical
Laikon General Hospital, Athens, Greece, 2Laboratory Microbiology, Akdeniz University, Antalya, Turkey,
of Cellular Signaling and Molecular Pharmacology,
3
Department of Pathology, Akdeniz University, Antalya,
Institute of Biosciences and Applications, National Turkey
Center for Scientific Research Demokritos, Athens,
Introduction: Hairy-cell leukemia (HCL) is a B-cell lymphop-
Greece, 3Department of Clinical Hematology,
roliferative disorder which is characterized by pancytopenia,
G. Gennimatas District General Hospital, Athens, Greece,
splenomegaly, characteristic cytoplasmic hairy projections and
4
First Department of Propedeutic Medicine, National and
a typical flow cytometric profile. The disease course is usually
Kapodistrian University of Athens, School of Medicine,
indolent and the current standard of care is treatment with purine
Athens, Greece
analogs. Cladribine is preferred initial therapy because of its ease
Objective: Signal Transducer and Activator of Transcription of administration and favorable toxicity profile.
(STAT) proteins have been intensively studied in hemato- Case: A73-year-old male patient was admitted with fever and
logic malignancies, and the efficacy of agents against STATs cough to our emergency department. He was hospitalized be-
in lymphomas is already under research. The correlation cause of community-acquired pneumonia and pancytopenia
of STATs with viral lymphomagenesis is being also actively (hemoglobin: 10.4 g/dl, leukocyte: 850/L, neutrophil: 580/L,
studied. The objective of the present study was to investigate platelet: 125000/L) and piperacillin tazobactam was started.
the expression of STAT5 and STAT5b in patients with Chronic Peripheral blood smear revealed cytoplasmic projections on
Lymphocytic Leukemia (CLL) in correlation to the presence medium size lymphocytes and CD19, CD20, CD25, CD11c and
of Epstein-Barr virus (EBV) and its major oncoprotein (Latent CD103 were positive with flow cytometric immunophenotyping.
Membrane Protein 1, LMP1). In the bone marrow biopsy, fat ratio was 70-80% and there was
Methods: We investigated the expression of total STAT5 and neoplastic infiltration of CD20, TRAP positive diffuse interstitial
STAT5b (by Western-blotting) in peripheral blood samples of small lymphoid cells. Patient was diagnosed with hairy-cell leu-
sixty three patients with CLL and fifteen healthy blood donors, kemia. Single course of cladribine for 7 seven days with a dose
in correlation to the presence of EBV (by RT-PCR for the BXLF1 of 0.1 mg/kg/day were started. After discharge he was readmit-
gene) and LMP1 (by PCR and ELISA). ted to inpatient setting due to febrile neutropenia and he was
Results: STAT5b was only expressed in patients (but not in healthy unresponsive to granulocyte-colony stimulating factor (G-CSF)
blood donors) and total STAT5 but particularly STAT5b expression and he had prolonged severe cytopenias. Bone marrow aspiration
was correlated to the presence of the virus (77.3% versus 51.2%, and biopsy revealed aplastic bone marrow without any infiltra-
p=0.006 for STAT5b) and to the expression of LMP1 (58.3% versus tion at second month of treatment. Other causes of acquired
21.6%, p=0.011 for STAT5b). Moreover, the expression of STAT5b aplastic anaemia were excluded. He became totally dependent
and the presence of EBV and LMP1 were strongly negatively on erythrocyte and platelet transfusions, and due to prolonged
correlated to the overall survival of the patients (log rank test severe neutropenia invasive pulmonary aspergillosis occurred.
p=0.011, 0.015, 0.006 respectively). Unfortunately, he died due to sepsis with multiple organ failure
Conclusion: This is, to our knowledge, the first report of a survival 3 months after cladribine administration.
disadvantage of EBV-positive patients with CLL, and this is the Conclusion: Treatment with purine analogues are well tolerated
first time that STAT5b expression is correlated to overall survival, in the majority of patients with HCL. Common side effects of
a correlation that was found to be stronger than that of overall cladribine are immunosuppression and reversible myelosuppres-
survival with the clinical stage of the disease in this group of sion. Recovery of peripheral blood counts may require weeks or
patients. The correlation of STAT expression with EBV along with even months. Cladribine associated irreversible bone marrow
our survival correlations defines a subgroup of patients with CLL aplasia is extremely rare in the literature.
with BMI. Our clinical prediction rule was adequately validated

HODGKINS LYMPHOMA regarding the prediction of BMI by either BMB or PET/CT. These
data suggest that BMB can be safely omitted in all patients with
P13 HL staged by PET/CT.
COMPARATIVE ASSESSMENT OF BONE MARROW
INVOLVEMENT (BMI) BY BM BIOPSY (BMB) OR
POSITRON EMISSION TOMOGRAPHY/COMPUTED
P14
TOMOGRAPHY (PET/CT) IN HODGKIN LYMPHOMA (HL) PET/CT FOR THE EARLY INTERIM EVALUATION OF
Theodoros VASSILAKOPOULOS1, Maria ANGELOPOULOU1, RESPONSE IN ADVANCED HODGKIN LYMPHOMA
Vassilios PRASSOPOULOS2, Sofia CHATZIIOANNOU3, (HL) AFTER ABVDX2: EFFECTIVE SALVAGE WITH
Vassilios SOTIROPOULOS4, Georgios BOUTSIKAS1, BEACOPP BUT LOW NEGATIVE PREDICTIVE VALUE
Gerassimos PANGALIS5, Panayiotis PANAYIOTIDIS6, FOR STAGE IV
Konstantinos KONSTANTOPOULOS1, Theodoros VASSILAKOPOULOS1, Phoebe RONTOGIANNI2,
Phoebe RONDOGIANNI7 Georgios BOUTSIKAS1, Ioannis ASSIMAKOPOULOS1,
1
Department of Hematology, National and Kapodistrian Sofia CHATZIIOANNOU3, Vassilios PRASSOPOULOS4,
University of Athens, School of Medicine, Athens, Greece, Gerassimos PANGALIS5, Panayiotis PANAYIOTIDIS6,
2
Department of Radiology and Nuclear Medicine, Hygeia Konstantinos KONSTANTOPOULOS1,
General Hospital, Athens, Greece, 3Department of PET/ Maria ANGELOPOULOU1
CT, Biomedical Research Foundation, Academy of Athens, 1
Department of Hematology, National and Kapodistrian
Athens, Greece, 4Department of PET/CT, Athens Medical University of Athens, School of Medicine, Athens, Greece,
Center, Athens, Greece, 5Department of Hematology, 2
Department of Nuclear Medicine, Evangelismos General
Athens Medical Center, Athens, Greece, 6First Department Hospital, Athens, Greece, 3Department of PET/CT,
of Propedeutic Medicine, National and Kapodistrian Biomedical Research Foundation, Academy of Athens,
University of Athens, School of Medicine, Athens, Greece, Athens, Greece, 4Department of Radiology and Nuclear
7
Department of Nuclear Medicine, Evangelismos General Medicine, Hygeia General Hospital, Athens, Greece,
Hospital, Athens, Greece 5
Department of Hematology, Athens Medical Center,
Athens, Greece, 6First Department of Propedeutic Medicine,
Objective: Recent data suggest that few HL patients have posi- National and Kapodistrian University of Athens, School of
tive BMB in the absence of PET/CT evidence for BMI. The aim of Medicine, Athens, Greece
this study was to correlate BMB with BM-PET/CT findings and
to assess the impact of our published clinical prediction rule Objective: A positive PET/CT after ABVDx2 (PET-2) is a highly
(Vassilakopoulos et al, Blood. 2005) on the frequency of BMI unfavorable prognostic factor in intermediate and advanced-
detected by either method. stage HL. We report here our experience with PET-2 in patients
Methods: PET/CT data were visually graded as follows: (1) no with truly advanced HL and evaluate its prognostic accuracy.
increased BM FDG uptake; (2) increased BM FDG uptake liver; Methods: 101 patients with advanced HL according to GHSG
(3) increased BM FDG uptake >liver; (4) solitary osseous/BM focus definition, who were treated with ABVD and underwent PET-2,
without CT correlate; (5) multiple osseous/BM foci. Patients were were retrospectively evaluated. PET-2 was assessed according
classified according to our clinical prediction rule for BMI in low-, to Deauville criteria (scores 4-5 considered positive). Switch to
standard- and high-risk groups. BEACOPP-esc was at the discretion of the treating physician.
Results: PET/CT and BMB data were available for 179 patients. Results: The median age of patients was 31.5 years (100/101 <60
PET/CT was negative for BMI in 148 and positive in 31 patients: years), 57% were males, 84% had NS-cHL, 40% and 52% were
4 had a single focus and 27 multiple foci. Only 14 patients had classified as stage IV by conventional and PET-based staging
BMI by BMB (7.8%). None of the patients of PET/CT categories respectively, and 67% had B-symptoms. The median IPS was 2;
1, 2, 3 or 4 had a positive BMB; 14/27 patients graded as 5 had 46% had IPS 3-7. PET-2 was negative in 77 and positive in 24 pa-
positive BMB (52%). The frequency of BMI by BMB and by PET/CT tients (24%). Overall, 3-year PFS was 76%. The strong prognostic
was 0%, 1.5%, 21.1% and 0%, 6.2% and 39.6% in low-, standard- value of PET-2 was verified (3-year PFS 86% in PET-2(-) vs. 43% in
and high-risk group respectively. The outcome of patients with PET-2(+) patients, p<0.0001), despite switch to BEACOPP-esc in
BMI by PET/CT was inferior (3-year PFS 56% vs 85%, p=0.001). 10/24 PET-2(+) patients (14 continued with ABVD). The 3-year PFS
Patients with diffuse FDG uptake >liver tended to have increased was 61% vs. 31% for PET-2(+) patients who received BEACOPP-esc
inflammatory activity (leukocytosis, anemia, elevated ESR and and ABVD respectively (p=0.059). Based on conventional staging
CRP, thrombocytosis). 3-year PFS did not differ between stage II-III and stage IV (89%
Conclusion: PET/CT is more efficient than BMB in detecting vs. 82% respectively, p=0.36). When initial staging was based on
BMI. There was no case of positive BMB in the absence of BMI PET/CT, the 3-year PFS was lower in stage IV compared to stage
by PET/CT. Increased diffuse BM FDG uptake is not associated II-III patients (77% vs. 94%, p=0.057).
Conclusion: The results of our study confirm the strong prog- better differentiate low risk group but it was able to discriminate
nostic value of PET-2, since the possibility of relapse was much OS more accurately in the high risk category compared to IPI.
higher in PET-2(+) patients, despite the more aggressive thera- Recently published study showed that, even though gene-based
peutic approach adopted for 10/24 of them. Patients treated with predictors have good discriminating ability when used alone, IPI
BEACOPP-esc upon PET-2(+) tended to have superior outcomes. remains the most powerful predictor in DLBCL patients. DLBCL
PET-2(-) patients with stage IV, as defined by baseline PET/CT, had is a heterogeneous disease and we will probably explore more
inferior outcomes. This observation may have significant impact molecular, immunohistochemical and clinical (NCCN-IPI?) pa-
on treatment design. rameters in the future. These efforts will contribute to develop
stronger risk classification process, maybe as a part of a never
ending story.
NON-HODGKIN LYMPHOMAS
P16
P15
HIGH BONE TURNOVER AND LOW BONE
COMPARISON OF IPI AND NCCN-IPI IN 324 DE-NOVO MINERAL DENSITY IS PRESENT IN PATIENTS
DLBCL PATIENTS: A MULTICENTER RETROSPECTIVE WITH NON-HODGKINS LYMPHOMA AFTER THE
ANALYSIS ADMINISTRATION OF FRONTLINE THERAPY
Erman ZTRK1, Murat ZBALAK2, Emin AVAR3, Konstantinos ANARGYROU1,
Anl DOLGUN4, Aye SALHOLU5, eniz NGREN5, Theodoros P. VASSILAKOPOULOS2,
Cem AR5, Zafer BALAR5, Teoman SOYSAL5, Dimitrios CHRISTOULAS1,Maria K. ANGELOPOULOU2,
Burhan FERHANOLU6 Maria DIMOU3, Athanasios PAPATHEODOROU4,
1
Ko University Hospital, Department of Hematology, Georgios BOUTSIKAS1, Panayiotis PANAYIOTIDIS3,
Istanbul, Turkey, 2Cerrahpaa Medical Faculty, Department Kostas KONSTANTOPOULOS2, Evangelos TERPOS5
of Internal Medicine, Istanbul, Turkey, 3Amerikan Hospital, 1
Department of Hematology, 251 General Air Force
Department of Oncology, Istanbul, Turkey, 4Hacettepe Hospital, Athens, Greece, 2Department of Hematology,
University, Department of Biostatistics, Ankara, Turkey, National and Kapodistrian University of Athens, School of
5
Cerrahpaa Medical Faculty, Department of Hematology, Medicine, Athens, Greece, 3First Department of Propedeutic
Istanbul, Turkey, 6Ko University Medical Faculty, Medicine, National and Kapodistrian University of Athens,
Department of Hematology, Istanbul, Turkey School of Medicine, Athens, Greece, 4Department of
Medical Research, 251 General Air Force Hospital, Athens,
Objective: Until recently, IPI was almost the only widely used
Greece, 5Department of Clinical Therapeutics, National
prognostic indicator in diffuse large B-cell lymphoma (DLBCL). IPI,
and Kapodistrian University of Athens, School of Medicine,
being developed in pre-rituximab era, fails to predict the prog- Athens, Greece
nosis in a considerable portion of patients with DLBCL. NCCN-IPI
was recently claimed to better predict the DLBCL outcomes. We Objective: The aim of the study was to evaluate the effects of
aimed to compare the prognostic significances of IPI and NCCN- chemotherapy on bone metabolism of patients with newly-
IPI in DLBCL patients treated with R-CHOP. diagnosed non-Hodgkins lymphoma (NHL).
Methods: All patients (n=324) diagnosed with DLBCL and treated Methods: Bone mineral density (BMD) of the lumbar spine (L1-L4)
with R-CHOP regimen and analysed retrospectively. and femoral neck (FN) of NHL patients was measured by DXA on
Results: Median follow-up was 3.7 years. Progressive free survival day 1/cycle 1 (baseline) and on day 30 of the last chemotherapy
and overall survival (OS) were compared between risk categories. cycle. The following bone metabolism markers were measured
5-year OS was 91% for both IPI and NCCN-IPI low risk groups on the days of DXA: i) osteoclast stimulators [sRANKL and osteo-
whereas 44% for IPI and 29% for NCCN-IPI high risk group. NCCN- protegerin (OPG)], ii) osteoblast regulators [PTH, vitamin-D, and
IPI and IPI have similar discriminations with concordance prob- dickkopf-1 (Dkk-1)], iii) bone resorption markers [CTX and TRACP-
ability estimates (CPE) (0,67 vs 0,68 respectively). There is a good 5b], and iv) bone formation markers [bone alkaline phosphatase
correlation with these two risk classification model determined (bALP) and osteocalcin (OC)].
with the weighted statistics (W=0.6817, p<0.001). Results: Fifty-three patients have completed the study to-date:
Conclusion: The authors indicated that NCCN-IPI provided 36 (67.9%) had diffuse large B-cell lymphoma, 5 (9.4%) fol-
increased capacity to discriminate both high-risk and low-risk licular (grade III), 4 (7.5%) mantle-cell, 6 (11.3%) marginal-zone
de-novo DLBCL patients. Huang et al justifying the better dis- and 2 (3.8%) T-cell NHL. Forty-seven patients (88.7%) received
crimination capacity of NCCN-IPI compared to IPI. Our report R-CHOP, 4 R-COP and 2 CHOP. At baseline, NHL patients had a
is based on the analysis of 324 de-novo DLBCL patients. Our median T-score of L1-L4 BMD of -0.63 (range: -4.27 to +3.68)
patients were treated in various hospitals, which reflect the real- and of FN BMD of -0.875 (-4.01 to +2.07). The administration of
life characteristic of our cohort. In our study, NCCN-IPI couldnt chemotherapy resulted in a dramatic reduction of BMD in L1-L4
(-1.12; -4.49 to +3.04; p<0.001) and in FN (-1.115; -3.68 to +1.12; albumin <4 g/dL, bulky disease, age-adjusted IPI (aaIPI).
p<0.001) compared to baseline. Patients who received 8 cycles Results: The median follow-up was 50 months. Among 52 fail-
of chemotherapy had a greater reduction of L1-L4 (p<0.001) ures, 51 occurred within 17 months from diagnosis. The 3-year
and FN (p=0.001) BMD. Chemotherapy also resulted in eleva- FFP was 75% and the 5-year OS 88%. The aaIPI (2) identified a
tions of CTX (p=0.017), TRACP-5b (p<0.001), bALP (p<0.001), OC minority of patients with a 5-year FFP of 64% vs. 79% for those
(p<0.001) and Dkk-1 (p=0.022) compared to baseline values. All with aaIPI 0-1 (p=0.04) and 5-year OS of 76% vs. 92% (p=0.003).
studied markers (except of sRANKL/OPG) were increased in NHL Many of the examined variables had a significant or borderline
patients post-chemotherapy compared to 30 healthy controls association with both FFP and OS. In multivariate analysis of OS,
(p<0.01). During study period, one male patient had a pathologi- extranodal involvement and bulky disease were independent PFs.
cal fracture in his right FN. OS at 5 years was effectively predicted, being 100%, 93% and
Conclusion: Frontline treatment (chemotherapy and/or ritux- 73% for patients with 0, 1 or 2 PFs respectively (p=0.0001). The
imab) results in high bone turnover, increased bone loss and corresponding 5-year FFP rates were 88%, 79% and 59% (p=0.002).
reduced BMD in NHL patients. The prophylactic use of bisphos- Conclusion: This is the largest series reported so far; RCHOPRT
phonates or denosumab may be useful for preventing bone loss provided satisfactory results in PMLBCL in terms of FFP and OS.
in these patients. The aaIPI was moderately predictive of the outcome. The com-
bination of extranodal involvement and bulky disease defined
a subgroup of patients with high risk of failure and death, who
P17 might be candidates for treatment intensification.
PROGNOSTIC FACTORS IN PRIMARY MEDIASTINAL
LARGE B-CELL LYMPHOMA (PMLBCL) UNDER
STANDARD CHEMOTHERAPY WITH RITUXIMAB-CHOP
P18
(R-CHOP) WITH OR WITHOUT RADIOTHERAPY (RT) PROGNOSTIC SIGNIFICANCE OF VON WILLEBRAND
Theodoros VASSILAKOPOULOS1, FACTOR ANTIGEN IN WALDENSTROMS
Maria ANGELOPOULOU1, Sotirios PAPAGEORGIOU2, MACROGLOBULINEMIA
Georgia KOURTI3, Evangelos TERPOS4, Evangelos TERPOS1, Efstathios KASTRITIS1,
Georgios BOUTSIKAS1, Konstantinos Ioannis PAPASSOTIRIOU2, Evangelos ELEUTHERAKIS-
KONSTANTOPOULOS1, Panayiotis PANAYIOTIDIS5, PAPAIAKOVOU1, Nikolaos KANELLIAS1,
Gerassimos PANGALIS6, Paraskevi ROUSSOU3 Michail MAZARAKIS2, Maria GAVRIATOPOULOU1,
1
Department of Hematology, National and Kapodistrian Magdalini MIGKOU1, Maria ROUSSOU1,
University of Athens, School of Medicine, Athens, Greece, Meletios A. DIMOPOULOS1
2
Second Department of Propedeutic Medicine, National 1
Department of Clinical Therapeutics, National and
and Kapodistrian University of Athens, School of Medicine, Kapodistrian University of Athens, School of Medicine,
Athens, Greece, 3Department of Internal Medicine, National Athens, Greece, 2Department of Clinical Biochemistry,
and Kapodistrian University of Athens, School of Medicine, Aghia Sophia Childrens Hospital, Athens, Greece
Athens, Greece, 4Department of Clinical Therapeutics,
National And Kapodistrian University of Athens, School of Objective: Patients with Waldenstroms Macroglobulinemia (WM)
Medicine, Athens, Greece, 5First Department of Propedeutic can manifest unique hemostatic disorders, including acquired
Medicine, National and Kapodistrian University of Athens, von Willebrand syndrome (AVWS), paraprotein-induced platelet
School of Medicine, Athens, Greece, 6Department of function defects, factor X deficiency, etc. Von Willebrand factor
Hematology, Athens Medical Center, Athens, Greece (vWF), a glycoprotein produced by the endothelial cells and
megakaryocytes, plays a key role in primary hemostasis but is
Objective: Prognostic factors (PFs) in PMLBCL have not been also a marker of endothelial stimulation. The aim of this study
extensively studied. Prior to the Rituximab era, the International was to evaluate vWF in WM and explore possible correlations
Prognostic Index (IPI) appeared to retain its prognostic signifi- with clinical data, including PFS and OS.
cance. R-CHOP provides very good results, but the applicability Methods: The analysis included 42 patients with symptomatic
of various PFs needs to be evaluated in order to define high risk WM and 19 healthy controls of matched gender and age. Ac-
patient subgroups, since more intensive chemotherapy might cording to IPSSWM, 22% had low, 43% intermediate and 35%
provide better results. Aim of the study was the identification of high risk WM, respectively. The vWF antigen (vWF Ag) levels
PFs in PMLBCL patients treated with RCHOPRT. were measured in serum collected before initiation of therapy
Methods: 213 patients with PMLBCL were treated with RCHOPRT. by means of a latex particle-enhanced immunoturbidimetric
The following potential prognostic factors were evaluated: Age, assay (HemosIL vWF antigen) with an automated coagulometer
gender, B-symptoms, stage III/IV, infradiaphragmatic disease, (ACL Top 3G, Instrumentation Laboratory, Lexington, MA, USA).
extranodal involvement, pleuritis, pericarditis, performance Results: Although the majority of WM patients had increased
status (PS) 2, LDH levels, anemia, leukocytosis, ESR 30 mm/h, levels of vW antigen, 6/42 (14%) had vWF Ag levels <40 U/L;
which could be compatible with AVWS. There was an inverse P20

correlation of platelet counts with levels of vWF Ag (R=-0.336,
p=0.032) and vWF Ag median was less frequent in patients with A YOUNG MAN WITH A PALPABLE MASS IN THE LEFT
low (11%) vs. patients with intermediate (59%) or high (62%) risk AXILLA
IPSS (p=0.036). Median follow up of symptomatic patients was Despoina BARBAROUSI, Nikolaos KANELLIAS,
4 years. Patients with vWF Ag levels within the upper quartile Enkeleida TRAIJE, Ioanna VARDOUNIOTI,
(i.e. vWF Ag 200 U/dL) had a median progression free survival Charis MATSOUKA, Konstantina PAPAIOANNOU
of 12 months vs. 63 months of patients with vWF Ag < 200 U/L Hematology Laboratory, Alexandra General Hospital, Athens,
(p<0.001). The median survival for patients with vWF Ag 200 Greece
U/dL was 37 months (4-year survival 29%) vs. 4-year survival of
97% for patients with vWF Ag <200 U/L (p<0.001). Introduction: Anaplastic large cell lymphomas (ALCLs) are a fre-
Conclusion: We conclude that serum vWF may become an im- quent subcategorie of Peripheral T-Lymphomas. A high fraction
portant prognostic marker in WM and needs further investigation of ALCLs are associated with translocations involving ALK, the
in larger cohort of patients. Anaplastic Lymphoma Kinase gene, located on chromosome 2p23.
We will describe a case of ALK+ T-Lymphoma in a young adolescent.
Case: A 19-year-old adolescent was referred to our Department
P19 because of a painful enlargement in the right axilla. Patients
history as well as family history were unremarkable. Clinical
RETROSPECTIVE EVALUATION OF OUTCOMES OF
examination revealed swelling in the left armpit (10 cm x 15 cm)
DA-EPOCH-R REGIMEN IN PATIENTS WITH ADVANCED
accompanied with ulceration and cellulitis and palpable lymph
STAGE NON-HODGKIN LYMPHOMA AND WITH HIGH
nodes in the left cervical region. Laboratory examination revealed
KI-67 EXPRESSION: SINGLE CENTER EXPERIENCE
only an elevated ESR (85 mm) with no other abnormal findings.
Pusem PATIR1,Hatice Demet Kiper UNAL1, In PET scan there was abnormal 18-FDG uptake (SUV max: 18.5)
Mustafa DURAN1, Terane NAGIYEVA2, in posterior cervical, left supraclavicular and subclavian Lymph
Ayhan DONMEZ1, Murat TOMBULOGLU1 nodes and a sizeable mass along the left lateral chest wall. Spleen
1
Ege University, Department of Hematology, Izmir, Turkey, also showed diffuse pathological uptake. Biopsy of the lymph
2
Ege University, Department of Internal Medicine, Izmir, Turkey nodes showed High grade Anaplastic large T-cell lymphoma
ALK positive. According to cotswolds modification of Ann Ar-
Objective: In most of CD 20(+) NHLs, rituximab-containing
bor staging system, patients stage was IISXBE with an IPI score
regimens mainly as R-CHOP have been defined as the standard
II. (low intermediate) Patient received 6 cycles of CHOEP. After
therapy. Recently, molecular and biological features of the tumor
those 6 cycles, PET SCAN was negative and the patient received
including Ki-67 expression have been described that have poten-
two more cycles of CHOP. After the completion of treatment, a
tial impact on outcome and treatment decissions. The purpose of
left spontaneous pneumothorax was diagnosed, which required
this study was to evaluate the efficiency and safety of the dose
surgical intervention.
adjusted etoposide, prednisolone, vincristine, doxorubicin, and
Conclusion: Our patient remains in complete response, three
cyclophosphamide with rituximab (DA-EPOCH-R) regimen on
years after completion of treatment. Several studies have shown
patients with Non-Hodgkin Lymphoma (NHL) with advanced
that ALCLs CD 30(+) ALK (+) represent a distinct clinicopathologic
stage and high Ki-67 expression.
entity and have a distinctly better clinical outcome than ALK -
Methods: Ten patients (5 female and 5 male) with Non-Hodgkin
systemic ALCLs. It is also known that normal serum LDH and an
Lymphoma were analyzed retrospectively who had received DA-
IPI score of 3 predicts a favorable clinical outcome.
EPOCH-R regimen. The characteristics of patients were illustrated
in table 1. The median age of patients was 49,7(17-76) years old.
All patients were stratified as in stage III/IV. Patients were treated P21
with 3-6 cycles of DA-EPOCH-R.
Results: The results showed that the overall response rate of PRIMARY AND SECONDARY LYMPHOMA
patients was 90%, including 9 patients (90%) in complete remis- INVOLVEMENT OF THE BREAST; TWO CASES
sion (CR) and 1 patient (10%) in stable disease (SD). At a median Hatice Demet KPER NAL1,Elvina DADASOVA1,
follow-up of 13,4 months. The major toxicity of DA-EPOCH-R Nazan ZSAN2, zgr MR3, Mahmut TB1
regimen was hematologic toxicity. Other toxicities were mild, 1
Ege University Medical Faculty, Hematology Department,
no treatment-related deaths occurred. Izmir, Turkey, 2Ege University Medical Faculty, Pathology
Conclusion: It is concluded that DA-EPOCH-R regimen is an ef- Department, Izmir, Turkey, 3Ege University Medical Faculty,
fective and safe protocol for the patients with NHL with advanced Nuclear Medicine Department, Izmir, Turkey
stage and high Ki-67 expression. More and comparative studies
are need to define the exact role of DA-EPOCH-R regimen in Introduction: Primary lymphoma of the breast is a rare form of
patients with poor molecular and biological features. NHL, representing approximately 0,5% of all breast malignan-
cies and 2,2% of all extranodal lymphomas. However, second- tomography (CT) showed mediastinal mass and pleural effusion
ary involvement of the breast with lymphoma is not unusual. and the bone marrow biopsy NMZL with bone marrow infiltra-
Diffuse Large B Cell Lymphoma (DLBCL) is the most common tion. He received four cycles of the combination of rituximab,
histopathological subtype. Here we report two cases of breast cyclophosphamide, doxorubicin, vincristine and prednisone (R-
lymphoma one is primary and the other is secondary, who both CHOP regiment), achieving partial response and then four more
achieved complete remission (CR) with standard chemotherapy. cycles. Soon after he relapsed. During his hospitalization lactate
Cases: Case 1: A 55-year-old woman presented with a painless left dehydrogenase (LDH) was elevated and he was diagnosed with
breast mass. Breast ultrasonography showed a non-homogeneous bone marrow necrosis. He received salvage therapy with ESHAP
mass in the left breast and a pathological lymph node in left regiment. Thirteen days later he presented with skin and eye
axilla. As the fine needle aspiration biopsy (FNAB) resulted nega- damage. Skin biopsy revealed Hematodermic Lymphoma. After
tive, segmental mastectomy was performed. Histopathological that he presented dyspnea and his chest computed tomography
diagnosis reported as DLBCL. In PET/CT; a few milimetric mild- revealed excessive mediastinal enlargement. He was treated with
metabolic jugulary and axillary LAPs were found. There wasnt radiotherapy but he quickly progressed to mixed phenotype
bone marrow infiltration. 2 cycles of R-EPOCH were performed acute leukemia and he died .
and CR achieved as control US showed no residual mass. It has Conclusion: NMZL comprises a biologically and clinically het-
planned to complete chemotherapy six cycles. erogeneous spectrum of lymphoma cases. Transformation to a
Case 2: A 36-year-old woman presented with servical mass and large B-lymphoma may occur. In our case the patient progressed
asymetrical tonsil hypertrophy; diagnosed as DLBCL by the to Hematodermic Lymphoma with mediastinal enlargement and
biopsy of left palatine tonsil. PET/CT showed multiple servical then to acute leukemia which is extremely rare. Since there are
and axillary LAPs and multiple hypermetabolic masses in right not yet specific diagnostic hallmarks and treatment consensus
and left breasts. Since the defined lesions were bilateral and guidelines for NMZL, we share our experience to this direction.
multifocal; lymphoma involvement was thought as the most
probable diagnosis. FNAB was performed from her right breast
but the results were non-diagnostic. There wasnt bone marrow P23
infiltration. After two cycles of R-CHOP, control PET/CT showed
PROGNOSTIC SIGNIFICANCE OF BODY MASS INDEX
anatomic and metabolic CR in breast lesions and LAPs. Chemo-
(BMI) IN PATIENTS WITH DIFFUSE LARGE B CELL
therapy was completed to eight cycles.
LYMPHOMA (DLBCL) TREATED WITH RITUXIMAB-
Conclusion: Lymphoma is the most common malignant disease
CHOP (R-CHOP) OR SIMILAR COMBINATIONS
metastatizing to the breast and rarely it presents as primary
breast involvement. Considering lymphoma in the differential
Theodoros VASSILAKOPOULOS1,
diagnosis of breast masses is important for developing an effec-
Sotirios PAPAGEORGIOU2, Maria ANGELOPOULOU1,
tive diagnostic and therapeutic approach.
Eugenia VERROU3, Maria MOSCHOGIANNIS4,
Christina KALPADAKIS5, Georgios BOUTSIKAS1,
Panayiotis PANAYIOTIDIS6, Gerassimos PANGALIS4,
P22 Konstantinos KONSTANTOPOULOS1
1
Department of Hematology, National and Kapodistrian
NODAL MARGINAL ZONE LYMPHOMA: OUR
University of Athens, School of Medicine, Athens, Greece,
EXPERIENCE IN A PARTICULAR CASE 2
Second Department of Propedeutic Medicine, National
Konstantina PAPAIOANNOU, Nikolaos KANELLIAS, and Kapodistrian University of Athens, School of
Despoina BARBAROUSI, Ioanna VARDOUNIOTI, Medicine, Athens, Greece, 3Department of Hematology,
Enkeleida TRAJCE, Charis MATSOUKA Theagenion Cancer Hospital, Thessaloniki, Greece,
Hematology Laboratory, Alexandra General Hospital, 4
Department of Hematology, Athens Medical Center,
Athens, Greece Athens, Greece, 5Department of Hematology, University
Hospital of Heraklion, Heraklion, Greece, 6First Department
Introduction: Nodal Marginal Zone Lymphoma (NMZL) is a of Propedeutic Medicine, National and Kapodistrian
primary nodal B-cell neoplasm that morphologically resembles University of Athens, School of Medicine, Athens, Greece
lymph nodes involved by MZL of extranodal or splenic types,
but without evidence of extranodal or splenic disease. Its rare, Objective: Recent data suggested that increased BMI correlates
approximately 1% of NHL cases. Nodal MZL usually progresses with favorable outcome in white American males with DLBCL,
to a higher grade histologic subtype, such as diffuse large B-cell while other studies provided controversial results. The aim of this
lymphoma. We present an unusual case of NMZL with transfor- study was the evaluation of the prognostic value of BMI in DLBCL.
mation to Acute Leukemia. Methods: 664 patients with DLBCL treated with R-CHOP or similar
Case: A 49-year-old man presented with a 3 week history of regimens were evaluated.
fever, cough and dyspnea. His physical examination revealed Results: The median BMI was 26.5 kg/m2, 156 (23%) patients
swollen lymph nodes in all anatomical sides, his chest computer were obese ( 30) and 273 (40%) overweight ( 25-29.9).
Increased correlated with increased age, while decreased BMI IX, and X levels were low. Autoimmune hemolytic anemia and
with PS 2, 2 E-sites and B-symptoms. 7-year PFS of patients hemophilia manifested in the patient and 48 mg/day metilpred-
with 30, 25-29.9 and <25 was 76%, 72% and 68% respec- nizolon was administered. During 6th day of therapy, hemolysis
tively (p=0.085 for 30 vs. <30). BMI had not prognostic and coagulation parameters of the patient were not recovered;
impact in patients <60 years. On the contrary, males >60 years his cryoglobulin level was 0.147 OD. The HCV, HBV, HIV antibodies
with 30 and females >60 years with 25 had more were negative. CHOP chemotherapy regime was used. However,
favorable outcomes than those with lower BMI. Similarly, in first week, he developed respiratory hemorrhage and died.
30 was a favorable prognostic factor only for patients without Conclusion: Autoimmune hemolytic anemia, immune trom-
B-symptoms. In multivariate analysis BMI had no independent bocytopenia, coagulation disorders, positive direct Coombs
prognostic impact in the whole patient population, while BMI are confirmed 10-20% patients suffering from SMZL. There is
30 was an independent prognostic factor in males >60 years a significant relation with SMZL and hepatitis-C virus. In our
(p=0.03) along with LDH and PS, and 25 was an indepen- case, cryoglobulinemia was present even though HCV was
dent prognostic factor along with LDH and stage III/IV in females negative. In SMZL patients with autoimmune hemolythic anemia
>60 years (p=0.055). In a preliminary analysis of 277 patients, and coagulation disorder, if steroid therapy does not benefit
DI of chemotherapy did not differ between patients with them,cryoglobulinemia should always come to mind. The real
30 or <30, while DI of Rituximab was slightly (but statistically treatment of cryoglobulinemia is treatment of the underlying
significantly) lower in obese patients (p=0.01). disease. For these patients chemotherapy must come to mind
Conclusion: The effect of BMI on prognosis appears to be re- urgently.
stricted to elderly DLBCL patients with different, possibly, cutoff
(30 vs 25 kg/m2) for males and females. This could not be attrib-
uted either to the unfavorable prognosis of patients with weight
loss, since the observation was restricted to patients without
MULTIPLE MYELOMA AND OTHER
B-symptoms, or to differences in DI of immunochemotherapy PLASMA CELL NEOPLASMS
according to BMI. A possible correlation with pharmacokinetic
parameters needs verification. P25
CIRCULATING LEVELS OF ADHESION MOLECULES IN
P24 206 PATIENTS WITH MULTIPLE MYELOMA: A SINGLE
CENTER PROSPECTIVE STUDY
A CASE OF SPLENC MARGNAL ZONE LYMPHOMA
Magdalini MIGKOU, Efstathios KASTRITIS,
WITH CRYOGLOBULINEMIA
Dimitrios CHRISTOULAS, Maria GAVRIATOPOULOU,
Yusuf DURMUS1, Mehmet Sevki UYANK2, Nikolaos KANELLIAS, Evangelos ELEUTHERAKIS-
Muhammet MADEN2, Gulsum Emel PAMUK2 PAPAIAKOVOU, Ioannis PANAGIOTIDIS,
1
Department of Internal Medicine, Edirne State Hospital, Maria ROUSSOU, Meletios A. DIMOPOULOS,
Edirne, Turkey, 2Department of Hematology, Trakya Evangelos TERPOS
University, Edirne, Turkey Department of Clinical Therapeutics, National and Kapodistrian
University of Athens, School of Medicine, Athens, Greece
Introduction: Splenic marginal zone lymphoma (SMZL) is B-cell
neoplasia, manifested by small cells and it targets white pulp fol- Objective: Interactions between plasma cells and cells in the bone
licles, bone marrow and peripheral blood cells. Cryoglobulinemia marrow microenvironment, through adhesion molecules, play a
is presence of cryoglobulins in the blood,which are abnormal im- key role in the biology of multiple myeloma (MM) and regulate
munoglobulins precipitating reversibly in low body temperature tumor growth, survival and migration in the bone marrow. The
(<37C). Autoimmune reactions may accompany SMZL. In this aim of our study was to evaluate the levels of soluble adhesion
report we aimed to present SMZL case with mmunolojc and molecules in patients with different plasma cell dyscrasias and
coagulation disorder. explore the correlations with disease characteristics, reported
Case: A 66-years-old male patient was diagnosed with SMZL after outcomes and how they are affected after treatment with novel
splenectomy performed 6 years ago. He applied with asthenia agents.
and weight loss. Physical examination revealed bilateral sub-knee Methods: Levels of circulating adhesion molecules VCAM-1,
purpuric eruption. Blood count resulted with hemoglobin 7.7 ICAM-1, P-, L- and E-selectin were measured with ELISA in serum of
g/dl, MCV 106 fl, WBC 24700 u/L, platelet 78000u/L, LDH 1286 47 patients with MGUS, 61 with AMM and 145 with symptomatic
u/L, haptoglobulin 32 mg/dl, reticulocyte 8.9%, also direct and MM. Same adhesion molecules were measured in serum of 87
indirect coombs were resulted positive.The prothrombin time patients with symptomatic disease at first relapse that received
was 34.6 seconds, INR 3.7, aPTT 51 seconds, and following val- second line therapy with novel agents, 47 received RD and 40 VD.
ues were found 1/1 dilution PT 22.3, INR 2.5, aPTT 51, the factor Measurements have been conducted before initiation of therapy
inhibitor test resulted positive. The patients factor II, VII, VIII, for newly diagnosed patients, or before the administration of the
first RD or VD, and after 4 cycles of therapy. one non-secretory and 5 light-chain MM. Bortezomib was given
Results: Patients with MM had increased levels of VCAM-1 and at the dose of 1.3mg/m2, iv or sc, in 3-week cycles, on days 1, 4,
ICAM-1 compared with MGUS, AMM patients and controls, while 8, and 11 of each cycle along with standard dose of dexametha-
the levels of selectins did not differ. Patients with ISS-1 had lower sone. The patients were assessed before treatment and after 4
circulating levels of VCAM-1 and higher circulating levels of P- cycles of treatment.
selectin. For MM patients, there was a positive correlation between Results: Fourteen (58%) patients had achieved a partial response,
VCAM-1 and ICAM-1, and a negative correlation between VCAM-1 while 2 (8%) patients had stable disease after 4 cycles of therapy.
and P-selectin. Serum VCAM-1 showed strong correlation with Cellularity was reduced in all patients after 4 cycles of treatment.
2-microglobulin and creatinine. P- and L-selectin negatively Plasma cell infiltration was reduced in 19 (79%) patients. Bcl-2
correlated with 2-microglobulin and creatinine. For patients was strongly positive in all pre-treatment biopsy specimens. This
with symptomatic disease median follow-up was 31 months, and strong positivity persisted even after the 4 cycles of bortezomib
median OS was 53 months. Median PFS was 23 months. Patients administration. Other immunophenotypic characteristics, includ-
with VCAM-1 >median had median PFS 19 months vs 32 months ing epithelial membrane antigen (EMA), CD79-alpha, and cyclin
of the others, and they also had median OS of 45 months vs 75 D1, have not altered following bortezomib treatment.
months. Patients with low P-selectin Conclusion: Previous studies with MM cell lines have suggested
Conclusion: Our study provides evidence about the role of that agents that reduce NF-kappaB also lower bcl-2 levels and
microenvironment in the biology of myeloma patients. VCAM- promote apoptosis. These results suggest that the anti-myeloma
1 had an independent prognostic value for both PFS and OS effect of bortezomib is independent of bcl-2.
in patients with newly-diagnosed symptomatic disease. Also
levels of ICAM-1 and VCAM-1 predicted for time to progression
in patients with asymptomatic disease. Reduction of VCAM-1 P27
and ICAM-1 after treatment with novel agents reveals an effect
THE RAPID RESOLUTION OF
of these drugs on the microenvironment, while Rd altered also
PSEUDOHYPERPHOSPHATEMIA IN AN IGA
the levels of all studied selectins suggesting an effect of Rd on
MULTIPLE MYELOMA PATIENT AFTER THERAPY WITH
the vascular niche and the endothelium.
A BORTEZOMIB-CONTAINING REGIMEN: A CASE
REPORT
P26 Muhammet MADEN1,Gulsum Emel PAMUK1,
Veysi Asoglu ASOGLU2, Omer Nuri PAMUK3
THE ANTI-MYELOMA EFFECT OF BORTEZOMIB IS 1
Department of Hematology, Trakya University,
INDEPENDENT OF THE BCL-2 STATUS
Edirne, Turkey, 2Department of Internal Medicine,
Dimitrios CHRISTOULAS, Efstathios KASTRITIS, Edirne State Hospital, Edirne, Turkey, 3Department of
Maria GAVRIATOPOULOU, Magdalini MIGKOU, Rheumatology,Trakya University, Edirne, Turkey
Despoina KALAPANIDA, Eftychia KAFANTARI,
Maria ROUSSOU, Flora ZAGOURI, Introduction: Hyperphosphatemia might be encountered in renal
Meletios A. DIMOPOULOS, Evangelos TERPOS failure, tumour lysis syndrome, hypoparathyroidism, pseudohy-
Department of Clinical Therapeutics, National and Kapodistrian poparathyroidism, lactic acidosis, and ingestion of exogenous
University of Athens, School of Medicine, Athens, Greece phosphate-containing sources. Hyperphosphatemia in multiple
myeloma (MM) is rare; and is expected when glomerular filtra-
Objective: The transcription nuclear factor-kappa B (NF-kappaB) tion rate (GFR) is <30 ml/min. We present a MM patient with
offers a significant survival potential in multiple myeloma (MM) pseudohyperphosphatemia.
cells. Bortezomib inhibits the degradation of IkappaB and hence Case: A 54-year-old male patient was admitted with weakness.
sequesters cellular NF-kappaB, blocking NF-kappaB transcrip- The laboratory analyses revealed anemia, hypoalbumenia, hyper-
tional activity, and thus it leads to reduced levels of growth globlunemia, hypercalcemia (10,1 mg/dl), hyperphosphotemia
factors and cell adhesion molecules. Bortezomib also enhances ( 20 mg/dl), GFR was 61 ml/min. Serum parathormone, vitamin
apoptosis in MM cells by bypassing anti-apoptotic mechanisms. D levels, the 24-hour calcium and phosphorus excretions were
Bcl-2 is an anti-apoptotic protein that confers unregulated growth normal. There was a monoclonal spike in the -region of serum
and resistance to conventional chemotherapy in MM cells. The protein electrophoresis. Serum IgA and kappa were, respectively,
aim of this study was to evaluate the effect of bortezomib on 6060 mg/dL and 5860 mg/dL. Serum immunoelectrophoresis
patients with relapsed/refractory MM regarding their bcl-2 status. showed monoclonal bands in IgA and regions. Bone marrow
Methods: We evaluated the immunophenotypic findings of my- aspiration revealed 22% plasma cells. He was diagnosed as stage
eloma cells in the bone marrow biopsies of 24 patients (14M/10F; III IgA MM according to International Staging System. He was
median age: 59 years, range: 35-71 years) who had received >4 given calcium acetata 500 mg three times a day for two days with
lines of treatment previously, including autologous stem cell no significant change in phosphorus level. He was administered
transplantation. Twelve patients had IgG MM, while 6 had IgA, VCD (bortezomib, cyclophosphamide, dexamethasone) protocol.
On the fifth day of VCD, phosphorus became 3.2 mg/dL, total to patients with higher CTX concentrations (not reached vs. 54
protein/albumin were 8.4/2.9 mg/dL. months respectively; p=0.034). This was more profound in patients
Conclusion: Hyperphosphatemia in MM might be explained treated with IMiDs-based regimens: the median survival of those
by the binding of paraprotein to phosphate or the interfer- with low CTX levels (<0.28 ng/ml) has not been reached yet vs.
ence of globulin fraction with colorimetric assays, resulting in 39 months of all others (p=0.02). On the contrary, in patients
falsely elevated phosphorus levels. Two ml of serum should who were treated with bortezomib-based therapies, high CTX
be deproteinized with 200 l of sulfosalicylic acid to remove could not define such a poor prognosis group.
the paraprotein. Our patient had no hypocalcemia, advanced Conclusion: Our study suggests that in the era of novel agents,
renal failure or any sign of hyperphosphatemia; so, considering only CTX, among 7 serum bone remodeling markers, correlated
pseudohyperphosphatemia we discontinued calcium acetate, with survival and could distinguish a subset of patients who
and instituted chemotherapy. He is the first reported MM patient receive frontline IMiDs-based therapies and have poor prog-
whose phosphorus normalized shortly after a bortezomib- nosis. This was not observed with bortezomib-based therapies,
containing regimen. In case of suspicion of pseudohyperphos- possibly due to the beneficial effect of bortezomib on bone
phatemia in MM; serum should be deproteinized and effective metabolism.
chemotherapy should be started to lower the paraprotein level.
Bortezomib-containing VCD protocol was observed to correct
pseudohyperphosphatemia rapidly. P29
BONE MARROW BIOPSY SHOULD BE CONSIDERED
FOR THE INITIAL EVALUATION OF INDIVIDUALS WITH
P28 ASYMPTOMATIC MONOCLONAL GAMMOPATHY AND
THE PROGNOSTIC VALUE OF C-TERMINAL CROSS- IMMUNOPARESIS OR MONOCLONAL COMPONENT
LINKING TELOPEPTIDE OF COLLAGEN TYPE-I (CTX) IN 1G/DL
PATIENTS WITH MULTIPLE MYELOMA Efstathios KASTRITIS,Evangelos TERPOS,
Dimitrios CHRISTOULAS, Efstathios KASTRITIS, Maria GAVRIATOPOULOU, Dimitrios CHRISTOULAS,
Nikolaos KANELLIAS, Magdalini MIGKOU, Evangelos ELEUTHERAKIS-PAPAIAKOVOU,
Maria GAVRIATOPOULOU, Maria GKOTZAMANIDOU, Magdalini MIGKOU, Despoina KALAPANIDA,
Evangelos ELEUTHERAKIS-PAPAIAKOVOU, Eftychia KAFANTARI, Maria ROUSSOU,
Dimitrios ZIOGAS, Meletios A. DIMOPOULOS, Meletios A. DIMOPOULOS
Evangelos TERPOS Department of Clinical Therapeutics, National and Kapodistrian
Department of Clinical Therapeutics, National and University of Athens, School of Medicine, Athens, Greece
Athens, Greece Objective: The aim of the study was to identify factors that could
aid in the evaluation of individuals presenting with asymptomatic
Objective: The aim of this study was to evaluate the impact of monoclonal gammopathy.
bone markers on the survival of multiple myeloma (MM) patients Methods: We analyzed the database of patients who were
who are treated upfront with novel agents. referred to our department for evaluation of asymptomatic
Methods: We studied 122 consecutive, unselected, newly di- monoclonal gammopathy. A bone marrow (BM) trephine biopsy,
agnosed patients with symptomatic MM who received upfront serum and urine protein electrophoresis with immunofixation
treatment with novel agents: 75 with IMiDs-based and 47 with and quantitative immunoglobulins are routinely performed in
bortezomib-based regimens. The circulating levels of the fol- all patients with monoclonal gammopathy.
lowing bone remodeling markers were evaluated at diagnosis: Results: Our analysis included 162 patients: 53% had a monoclonal
i) osteoclast regulators: sRANKL and osteoprotegerin (OPG); IgG, 15.5% IgA, and 24% IgM, while 4% had a biclonal paraprotein;
ii) osteoblast inhibitor dickkopf-1 (Dkk-1); iii) bone resorption 63% had a kappa light chain. The median serum M-protein was
markers: CTX and TRACP-5b; and iv) bone formation markers: 0.95 g/dl (range 0.1-2.99 g/dl) and was higher in those with IgG or
bone-specific alkaline phosphatase (bALP) and osteocalcin. IgA vs. those with IgM (p=0.009). Immunoparesis of at least one of
Results: At diagnosis, MM patients had increased serum con- the uninvolved immunoglobulins was present in 38% and of both
centrations of sRANKL, OPG, CTX, TRACP-5b, Dkk-1 and sRANKL/ of the uninvolved immunoglobulins in 6% of patients. Median
OPG ratio and decreased levels of bALP compared to 30 controls infiltration by monoclonal cells in BM biopsy was 7% for those
(p<0.01), while their levels correlated with the extend of bone with an IgM-gammopathy and 15% for those with monoclonal IgG
disease. The median survival of all patients was 59 months. In or IgA (p=0.047). There was a significant correlation of the size of
the univariate analysis, among the studied bone markers, only M-protein and of the BM infiltration (R=0.592, p<0.001). Among
CTX, as a continuous variable, was predictive of survival (HR: those with M-protein<0.5 g/dl, 11% had10% clonal cells in their
1.292, p=0.024). Patients with low CTX concentrations (<0.28 BM biopsies while the respective rates were 88% for those with
ng/ml; lower quartile; N=29) had superior survival compared M-protein 1 g/dl and 97% for M-protein 2 g/dl. Immunoparesis
of at least one of the uninvolved immunoglobulins was associated profound in those who achieved very good partial response
with 10% BM clonal cells in 90% of patients. In regression analysis, (vgPR; p=0.04). No alterations regarding T subpopulations or
immunoparesis of at least one of the uninvolved immunoglobu- cytokines was observed. Significant correlations between disease
lins (OR:6.45, 95%CI:2.32-18, p<0.001), an IgG or IgA monoclonal characteristics and Tregs were not observed in either group of
protein (OR:2.67, 95%CI:1.1-6.4, p=0.028) and an M-protein 1 g/ patients. In the cox regression analysis, Tregs % did not correlate
dl (OR:5.4, 95%CI:2.23-13) were independently associated with with progression-free survival (PFS).
10% clonal infiltration in BM biopsy. Conclusion: We have demonstrated that Tregs % are significantly
Conclusion: BM biopsy can reveal asymptomatic myeloma or reduced after treatment with Rd especially in patients with vgPR,
Waldenstroms Macroglobulinemia that may escape identification suggesting a possible relation of immune surveillance with quality
with standard criteria and should be included in the initial workup of response. However, PFS was not affected in the current study.
of individuals with asymptomatic monoclonal gammopathy. Bortezomib-based treatment has no impact on Tregs number or
function. No relation between Tregs % and relative cytokines was
proved in the current study, indicating the unexplored immune
P30
mechanisms underlying MM.
T-REGULATORY CELLS ARE SIGNIFICANTLY REDUCED
AFTER TREATMENT WITH LENALIDOMIDE, BUT NOT
WITH BORTEZOMIB, AND CORRELATE WITH THE P31
ACHIEVEMENT OF AT LEAST VGPR IN PATIENTS WITH
LACK OF SURVIVAL IMPROVEMENT WITH NOVEL
MULTIPLE MYELOMA
ANTI-MYELOMA AGENTS FOR PATIENTS WITH
Christina HADJIAGGELIDOU1, Evangelos TERPOS2, MULTIPLE MYELOMA AND CENTRAL NERVOUS
Evdokia MANDALA3, Dimitra MARKALA1, SYSTEM INVOLVEMENT: THE GREEK MYELOMA
Eythimia GIANNAKI1, Athanasios PAPATHEODOROU4, STUDY GROUP EXPERIENCE
Sofia VAKALOPOULOU5, Pavlina KONSTANTINIDOU1,
Meletios A. DIMOPOULOS2,Eirini KATODRITOU1 Eirini KATODRITOU1, Evangelos TERPOS2,
Sossana DELIMPASI3, Argiris S. SYMEONIDIS4,
1
Department of Hematology, Theagenion Cancer Hospital, Marie-Christine KYRTSONIS5, Chrysa VADIKOLIA6,
Thessaloniki, Greece, 2Department of Clinical Therapeutics,
Michael MICHAEL7, Maria KOTSOPOULOU8,
National and Kapodistrian University of Athens, School of
Pavlina KONSTANTINIDOU1, Meletios A. DIMOPOULOS2
Medicine, Athens, Greece, 3Fourth Department of Internal
Medicine, Aristotle University of Thessaloniki, School of
1
Department of Hematology, Theagenio Cancer Hospital,
Medicine, Thessaloniki, Greece, 4Department of Medical Thessaloniki, Greece, 2Department of Clinical Therapeutics,
Research, 251 General Air Force Hospital, Athens, Greece, National and Kapodistrian University of Athens, School of
5
Second Propedeutic Department of Internal Medicine, Medicine, Athens, Greece, 3Department of Hematology and
Aristotle University of Thessaloniki, School of Medicine, Bone Marrow Transplantation Unit, Evangelismos Hospital,
Thessaloniki, Greece Athens, Greece, 4Hematology Division, Department of
Internal Medicine, University of Patras Medical School,
Objective: Immune dysfunction is an important feature of Patras, Greece, 5First Department of Propedeutic Medicine,
multiple myeloma (MM) and has been associated with reduced National and Kapodistrian University of Athens, School
survival. Studies have shown that regulatory T cells (Tregs) are of Medicine, Athens, Greece, 6Department of Hematology,
implicated in the immune surveillance of different tumors, includ- 424 General Military Hospital, Thessaloniki, Greece,
ing MM. Data regarding alterations of Tregs during therapy with 7
Department of Hematology, General Hospital of Nicosia,
novel agents (NA), i.e. bortezomib and lenalidomide, are limited. Nicosia, Cyprus, 8Department of Hematology, Metaxa
Our aim was to explore the alterations of Tregs and T subpopula- Cancer Hospital, Piraeus, Greece
tions (i.e. T4, T8, NK, NK-like), as well as changes in the levels of
cytokines related to Tregs function and MM biology (IL-6, IL-2, Objective: Multiple myeloma of the central nervous system
IL-17, TGF-), during treatment with NA and to explore possible (CNS-MM) is a rare extramedullary manifestation of MM. It oc-
correlations with disease characteristics and response parameters. curs in less than 1% of MM cases and exhibits a dismal prognosis
Methods: We evaluated 29 patients with symptomatic MM, at di- with overall survival (OS) of less than 6 months. The purpose of
agnosis or relapse (M/F: 15/14, median age: 61 years, range: 39-77 the current study was to describe the incidence, the clinical and
years). Eleven patients received bortezomib-dexamethasone (BD) laboratory characteristics, the response to treatment, the out-
(group A) and 18 patients received lenalidomide-dexamethasone come and the possible prognostic factors of CNS-MM survival,
(Rd) (group B). The median number of previous treatment lines in the era of novel agent-based combinations (NAC). To our
was 1 (0-3). knowledge this is one of the largest studies including CNS-MM
Results: In group A, no significant alterations of Tregs %, T sub- patients treated in the vast majority with NAC and mostly with
populations or cytokines was observed. In group B, there was bortezomib-based combinations.
a significant reduction of Tregs % (p<0.001) and this was more Methods: We retrospectively reviewed the medical records of
30 consecutive patients with CNS-MM, diagnosed and treated years, range: 47-72 years) out of 648 consecutive MM patients
in 12 Centers of the Greek Myeloma Study Group. who were diagnosed between 1989 and 2013. LTS were younger
Results: Between January 2000 and December 2013, 31 (0.9%) out and most of them presented with ISS stage I/II compared to all
of 3408 newly diagnosed symptomatic MM patients, consecutively others (p<0.001). LTS had higher hemoglobin, lower creatinine
diagnosed and treated during the same period developed CNS- and lower beta2-microglobulin at diagnosis compared to controls
MM (M/F: 15/16, median age: 59 years, range: 20-96 years; newly (p <0.05). Bence-Jones proteinuria and immunoparesis at diagno-
diagnosed/relapsed-refractory: 2/29; median time to CNS-MM sis presented less frequently in LTS; recovery of immunoparesis
diagnosis: 29 months). Twenty-six percent of patients had circulat- after 1st line treatment was more common in LTS (p <0.05). 72%
ing plasma cells (PCs) or plasma cell leukemia (PCL) at the time of of LTS received novel agents (NA) during the course of MM. The
CNS-MM diagnosis and 39% had skull-derived plasmacytomas, number of patients treated with NA and the response rate after
suggesting hematological and contiguous spread. Treatment for 1st line therapy did not differ between LTS and the other patients;
CNS-MM was offered in 29/31 patients and 11/29 responded (NAC: LTS received more frequently autologous transplantation at 1st
18/29, additional radiotherapy: 9/28, intrathecal chemotherapy: line and NA at 2nd line treatment compared to all other patients
13/29). The median post CNS-MM survival was 3 months (95% (p <0.05). After a 12-year median follow-up (range: 2-180 months),
CI: 1.9-4.1) and did not differ between patients treated with NAC 28/50 LTS vs. 84/598 of other MM patients were alive (p <0.001);
and/or radiotherapy vs. others. In the multivariate analysis, prior 22 LTS patients died (due to MM: 13 patients, irrelevant causes:
treatment of MM with NAC, extramedullary disease (EMD) during 9 patients); 12/28 alive LTS were in CR during evaluation. The
MM course (i.e. plasmacytomas, circulating PCs or documented median PFS and OS for LTS vs. other patients was 81 months
PCL) and abnormally high LDH at MM diagnosis were independent (95% CI: 56-105) vs. 17 months (95% CI: 15-19) and 200 months
prognostic factors, whereas treatment of CNS-MM with NAC did (95% CI: 180-219) vs. 33 months (95% CI: 30-36), respectively
not predict for post CNS-MM survival. (p<0.05). In the multivariate analysis, PFS-2 was the only posi-
Conclusion: Despite the relatively limited number of patients tive predictor for long-term survival (p <0.001; HzR: 0.98. 95% CI:
due to the rarity of CNS-MM, our results suggest that NAC do 0.96-0.99); 28% of patients with PFS2 4 years were alive after 10
not seem to improve post CNS-MM survival. Patients with EMD years compared to 0.4% of those with PFS2 <4 years.
display shortened post CNS-MM survival and should be followed Conclusion: In conclusion, the percentage of LTS has increased
thoroughly. in the era of NA. LTS present with more favorable disease char-
acteristics compared to other MM patients. PFS-2 was the most
significant prognostic factor of long-term survival, suggesting that
P32 disease control during the initial phase of MM, where sensitive
clones still prevail and when there is no drug resistance, should
PROGRESSION-FREE SURVIVAL 2 (PFS-2) IS THE MOST
be the main goal of the treatment strategy. Finally, about 1/3 of
SIGNIFICANT PROGNOSTIC FACTOR OF LONG-TERM
patients who displayed disease control of 4 years after 2 treat-
SURVIVAL IN THE ERA OF NOVEL AGENTS: A SINGLE
ment lines, enjoyed a long-term survival and most importantly,
MYELOMA CENTER EXPERIENCE
1/3 of them remained in CR and could be considered as cured
Eirini KATODRITOU1,Nikos SPYRIDIS1, Sofia PAPADAKI1, from MM, challenging the dogma of incurable disease.
Evlambia GIANNOPOULOU1, Vassiliki PALASKA1,
Dimitra MARKALA1, Evgenia VERROU1,
Christina HADJIAGGELIDOU1, P33
Pavlina KONSTANTINIDOU1, Evangelos TERPOS2
CHANGES IN CHROMATIN STRUCTURE AND KEY-
1
Department of Hematology, Theagenion Cancer Hospital,
MOLECULES OF THE DNA DAMAGE RESPONSE
Thessaloniki, Greece, 2Department of Clinical Therapeutics,
PATHWAYS AFFECT THE TRANSFORMATION
PROCESS OF MYELOMAGENESIS AND THE OUTCOME
Medicine, Athens, Greece
OF ANTI-MYELOMA THERAPY
Objective: Before the era of novel agents (NA), 3-4% of Multiple Maria GKOTZAMANIDOU1, Evangelos TERPOS1,
myeloma (MM) patients were considered as long-term survivors Meletios A. DIMOPOULOS1, Vassilis L. SOULIOTIS2
(LTS) (i.e. patients remaining alive for >10 years). Herein, we 1
describe the incidence, characteristics and prognostic factors Kapodistrian University of Athens, School of Medicine,
of LTS MM patients of a Greek hematology center. Athens, Greece, 2Institute of Biology, Medicinal Chemistry
Methods: We checked the database of our center for the pres- and Biotechnology, National Hellenic Research
ence of LTS. In addition to Progression Free Survival (PFS) and Foundation, Athens, Greece
overall survival (OS), we evaluated PFS2, defined as the time
from MM diagnosis to second objective disease progression, or Objective: Important anticancer drugs exert their antitumor
death from any cause. effects through the production of DNA interstrand cross-links
Results: We identified 50 LTS (7.7%; M/F: 23/27, median age: 65 (ICLs). However, the precise mechanisms contributing to differ-
ential response of patients to chemotherapy with these drugs investigate a possible association between SNPs in CYP2C8
are poorly understood. and PPAR- and the risk of developing ONJ in a large number of
Methods: DNA damage response (DDR) signals, chromatin multiple myeloma (MM) patients who received zoledronic acid
structure and transcriptional activity were examined following ex (ZA) for their bone disease.
vivo melphalan treatment of peripheral blood mononuclear cells Methods: We screened 36 patients who developed ONJ and
(PBMCs) from 25 healthy controls (HC) and 15 newly-diagnosed 104 patients who did not develop ONJ for the SNPs of interest
multiple myeloma (MM) patients, responders (PR, n=9) and in PPAR- (rs1152003) and CYP2C8 (rs193495) genes by direct
non-responders sequencing of peripheral blood derived DNA.
Results: The accumulation of monoadducts was inversely correlat- Results: The median follow up of the patients was 72 months
ed with the first-phase repair capacity of PBMCs, being significantly and the median time to ONJ development was 47 months (range:
higher in HC than in responders and lowest in non-responders 7-182 months). Patients who developed ONJ had a median of 31
(P<0.001). Also, although ICL unhooking rates were similar in all ZA infusions versus 25 infusions for the others. However, 31% of
individuals, accumulation of ICLs was significantly higher in HC patients who developed ONJ had received <24 ZA infusions. An
compared to responders (P<0.01), due to higher levels of mono- extraction preceded the development of ONJ in 60% of patients,
adducts (precursors of ICLs) left unrepaired in PBMCs. Minimal it was unprovoked in 20% and it was associated with trauma/
amounts of ICLs were observed in non-responders. Moreover, DSBs inflammation in 20% of patients. In patients with <24 infusions
burden was significantly higher in HC than in responders PBMCs, of ZA, the presence of SNPs in both PPAR- and CYP2C8 was
due to higher accumulation of ICLs (precursors of DSBs) and lower associated with a significantly higher probability of ONJ devel-
rates of DSBs repair in these cells (P<0.01). Minimal amounts of opment (55% versus 16%, p=0.011 and 29% versus 7%, p=0.07,
DSBs were observed in non-responders. Interestingly, apoptosis respectively) and a shorter time to development of ONJ (19 versus
rates were inversely correlated with the DSBs repair efficiency of 69 months, p<0.001 for PPAR-). Combining the genotype risk,
PBMCs, being significantly higher in HC compared to responders those with high risk of SNPs in both genes had a 70% cumulative
and lowest in non-responders (P<0.05). An inverse correlation was incidence of ONJ within 24 months from initiation of ZA versus
found between the chromatin condensation and the repair capac- 17% for those carrying one of the two SNPs and 0% for those
ity of PBMCs, with the looseness of the chromatin structure being without any high risk of SNPs (p<0.001).
significantly higher in non-responders compared to responders Conclusion: We conclude that SNPs in the CYP2C8 and PPAR-
and lowest in HC (P<0.05). Finally, an altered expression of several genes are associated with a risk of early development of ONJ.
DNA damage response-related genes was found between HC and However, increasing cumulative dose of ZA increases substan-
MM patients as well as between responders and non-responders. tially the risk of ONJ in all patients, independently of genotype-
Conclusion: Changes in chromatin structure and key-molecules defined risk.
of the DDR pathways affect the repair capacity of MM patients,
thus contributing to both myelomagenesis and the outcome of
anti-myeloma therapy. P35
CENTRAL NERVOUS SYSTEM RELAPSE AFTER
CHEMOTHERAPY IN A PATIENT WITH MULTIPL
P34 MYELOMA
EARLY DEVELOPMENT OF OSTEONECROSIS OF THE erife Solmaz MEDEN1,Ferda BLGR2, Can ZL1,
JAW IN PATIENTS WITH MULTIPLE MYELOMA WHO Sinem NAMDAROLU1, Tugba ETNTEPE1, Oktay BLGR1
RECEIVE ZOLEDRONIC ACID THERAPY: THE ROLE OF 1
Department of Hematology, Bozyaka Training and
GENETIC FACTORS
Research Hospital, zmir, Turkey, 2Department of Internal
Pelagia MELEA1, Evangelos TERPOS2, Tina BAGRATUNI2, Medicine and mmunology, Katip Celebi University, Ataturk
Evangelos ELEUTHERAKIS-PAPAIAKOVOU2, Training and Research Hospital, zmir, Turkey
Maria GAVRIATOPOULOU2, Ioannis PANAGIOTIDIS2,
Ioannis MELAKOPOULOS1, Christina TESSEROMATIS3, Introduction: We report a case of central nervous system relaps
Efstathios KASTRITIS2, Meletios A. DIMOPOULOS2 with intraparancimal,dural and leptomeningeal involvement
1
Department of Maxillofacial Surgery, Henry Dunant after high dose chemotherapy.
Hospital, Athens, Greece, 2Department f Clinical Case: A 72-year-old man received two cycles of bortezomib
Therapeutics, National and Kapodistrian University of and dexamethasone as an induction treatment for stage IIIA
Athens, School of Medicine, Athens, Greece, 3Department IgA kappa multipl myeloma. Partial response achieved after
of Pharmacology, National and Kapodistrian University of two cycles of bortezomib and dexamethazone and continued
Athens, Faculty of Medicine, Athens, Greece to treat. Biphosphonate treatment was given because of lytic
bone lesions. Four months after bortezomib and dexamethasone
Objective: One of the complications of bisphosphonates is terapy increased plasma cells in the bone marrow was observed.
osteonecrosis of the jaw (ONJ). The aim of this study was to Patients were considered refractory multiple myeloma and began
therapy with lenalidomide and dexamethasone. Two months patients had bone marrow infiltration >60%. Hypercalcemia,
after lenalidomide -dexamethasone therapy the patient admitted immunoparesis and thrombocytopenia presented more rarely
with sudden trensient loss of vision,headache. Cranial computer (20%). Two patients presented the same clonality at CLL and at
tomography imaging revealed mass lesion occupying bilateral MM diagnosis. One patient had kappa-restricted CLL cells and
frontal lobes, was determined mega cisterna magna, both cerebral lamda-restricted myeloma cells, while in the two last ones the CLL
hemispheric cortical sulci were detected especially in the pari- light chain restriction was unclear. At the time of MM diagnosis,
etooccipital expanded to be more specific. Heterogenous dural bone marrow biopsy revealed 2 distinct populations (60%) or
and leptomeningeal infiltration was detected. After lenalidomide total infiltration by CLL (20%) or MM (20%) cells.
therapy symptoms related with central nervous system involve- Conclusion: MM can occur late at the course of CLL, with severe
ment and cytopenias related bone marrow infiltration got worse. manifestations. One case presented clearly 2 different clones,
The patient was lost from sepsis and renal failure. while for the others, IgH rearrangement studies need to be done
Conclusion: Central nerveus system involvement of multipl in order to understand the biology of this coexistence.
myeloma is rare. It may manifest is dural myeloma or intrapa-
renchymal infiltration or with diffuse leptomeningeal involve-
ment. n the literature there is no standart therapeutic approach P37
regarding the central nervous system relapse after high dose
SKELETAL-RELATED EVENTS REMAIN A SIGNIFICANT
therapy and median survival of patients with cns relapse is 2 to
COMPLICATION OF MULTIPLE MYELOMA EVEN IN
3 months. There are no treatment guideline for central nerveus
THE ERA OF NOVEL AGENTS
system myelomatosis in the literature. Systemic chemotherapy
regimes, radiotherapy and intrathecal chemotherapy were tried,
Evangelos TERPOS, Nikolaos KANELLIAS,
but thy have not prolonged survival. The central involvement of
Dimitrios CHRISTOULAS, Maria GAVRIATOPOULOU,
myeloma patient is presented for contributions to the literature.
Despoina FOTIOU, Dimitrios ZIOGAS,
Evangelos ELEUTHERAKIS-PAPAIAKOVOU,
Eftychia KAFANTARI, Efstathios KASTRITIS,
P36 Meletios A. DIMOPOULOS
PATIENTS WITH CONCURRENT CHRONIC LYMPHOCYTIC
LEUKEMIA (CLL) AND MULTIPLE MYELOMA (MM)
Athens, Greece
Eftychia NIKOLAOU1,Paraskevi PAPAIOANNOU1,
Tatiana TZENOU1, Anastasia POULI2, Sotiria KOTSANTI1, Objective: The aim of this study was to evaluate the SREs inci-
Panayiota PETSA1, Maria DIMOU1, Theodoros ILIAKIS1, dence in the era of novel agents.
Panayiotis PANAYIOTIDIS1, Marie-Christine KYRTSONIS1 Methods: We retrospectively evaluated 400 consecutive patients
1
National and Kapodistrian University of Athens, School with symptomatic MM (207M/193F, median age: 63 years). All
of Medicine, Laikon General Hospital, Athens,Greece, patients had a whole-body skeletal survey using conventional
2
Department of Hematology, Agios Savvas Anticancer radiography at diagnosis and then at the time of relapse or
Hospital, Athens, Greece whenever clinically indicated.
Results: At diagnosis, the skeletal survey detected osteolytic
Objective: MM and B-cell CLL are two distinct lymphoproliferative disease in 284 (71%) patients. SREs were observed in 167 (41.7%)
disorders that arise at different stages of the B-cell maturation patients at diagnosis: 104 (26%) patients presented with patho-
pathway. Their coexistence has sporadically been reported, with logical fractures, while 22 (5.5%) patients required surgery to
their clonal relationship being controversial. bone, 21 (5.2%) radiotherapy and 20 (5%) patients presented with
Methods: We report a series of 5 patients with similtaneous SCC. The incidence of SREs was higher in patients with osteolytic
CLL/MM. lesions (49.5% vs. 24%, p<0.001). However, approximately 25% of
Results: 5 patients (60% females) were diagnosed as symptomatic patients without lytic lesions presented with a SRE at diagnosis.
MM 7 years (4-10) after the initial diagnosis of CLL. Mean age During first line treatment, 7 (1.75%) patients developed a SRE:
at CLL and MM diagnosis was 68 (63-73) and 75 (67-79) years 2 on bortezomib- and 5 on IMiD-based regimens. The median
respectively. Adverse prognostic factors at the time of CLL di- follow-up was 39 months. At the time of first relapse (n=176), 3
agnosis were unmutated CLL (60%), CD38+ (40%) and complex patients presented with fractures and 35 patients required local
caryotype (20%). 60% of patients had received at least one CLL radiotherapy to bone (SRE incidence: 21.6%). Patients who had
therapy-line, while all the patients were stable, with a long follow received only bortezomib-based regimens (VD or VCD, n=20)
up period before developing MM . MM type was IgG (60%), LC had lower SRE rate (2/20, 10%) vs. all others (36/156, 22%). In
(20%) and IgD (20%), while patients DS stage was III (100%) and total, during the course of their disease, 52.8% of the patients
ISS stage was II (40%) and III (60%). Most common symptoms presented with at least one SRE. Presentation with SREs at di-
were: bone disease with multiple fractures (80%), anemia (60%), agnosis did not predispose for SREs during the disease course,
severe renal failure (60%) requiring hemodialysis (40%). 60% of regardless of anti-myeloma treatment, possibly due to the low
number of fractures and the higher number of radiation needed variable and as dichotomous variable, in this cohort of patients.
after frontline therapy. Conclusion: We conclude that serum TIMP-1 is not elevated in
Conclusion: SREs remain a significant complication of MM. De- myeloma patients at first relapse although its levels correlate
spite high response rates after frontline therapy >20% of patients with abnormal bone remodeling and ISS. This may be due to the
required radiotherapy at the time of relapse. The fracture rate continuous use of zoledronic acid in our patients.
was low during first line therapy and at first relapse probably
due to the extensive use of BPs and bortezomib, which has bone
anabolic effects. P39
VEGFR-1 CORRELATES WITH INCREASED MICROVESSEL
DENSITY AND INFERIOR SURVIVAL IN NEWLY
P38 DIAGNOSED PATIENTS WITH MULTIPLE MYELOMA
CIRCULATING TISSUE INHIBITOR OF Gerasimos-Petros PAPASSOTIRIOU1,
METALLOPROTEINASE-1 CORRELATE WITH Efstathios KASTRITIS2, Evangelos ELEUTHERAKIS-
ADVANCED STAGE AND ABNORMAL BONE PAPAIAKOVOU2, Filia APOSTOLAKOU1,
REMODELING IN MULTIPLE MYELOMA PATIENTS AT Maria GKOTZAMANIDOU2, Despoina FOTIOU2,
FIRST RELAPSE WHO RECEIVE THE COMBINATION OF Ioannis PANAGIOTIDIS2, Ioannis PAPASSOTIRIOU1,
LENALIDOMIDE AND DEXAMETHASONE Meletios A. DIMOPOULOS2,Evangelos TERPOS2
Evangelos TERPOS, Magdalini MIGKOU, 1
Department of Clinical Biochemistry, Aghia Sophia
Dimitrios CHRISTOULAS, Maria GAVRIATOPOULOU, Childrens Hospital, Athens, Greece, 2Department of Clinical
Despoina FOTIOU, Ioannis PANAGIOTIDIS, Therapeutics, National and Kapodistrian University of
Dimitrios ZIOGAS, Maria ROUSSOU, Athens, School of Medicine, Athens, Greece
Efstathios KASTRITIS, Meletios A. DIMOPOULOS
Department of Clinical Therapeutics, National and Kapodistrian Objective: The aim of the study was to evaluate placental growth
University of Athens, School of Medicine, Athens, Greece factor (PlGF) and vascular endothelial growth factor receptor-1
(VGFR-1) in symptomatic multiple myeloma (MM), compare the
Objective: Tissue inhibitors of metalloproteinases (TIMPs) are results with asymptomatic MM and MGUS and explore possible
endogenous inhibitors of metalloproteinase activities and thus correlations with marrow angiogenesis (microvessel density,
they modulate matrix metalloproteinase function and suppress MVD) and survival.
extracellular matrix turnover. Pre-treatment serum TIMP-1 is Methods: Circulating levels of PlGF and VEGFR-1 were measured
associated with advanced myeloma but there is no information in 64 patients with newly diagnosed MM (16 with asymptomatic
for the role of TIMP-1 at the time of relapse. MM and 48 with symptomatic MM), 8 with MGUS and 20 healthy
Methods: Circulating TIMP-1 levels were evaluated in 36 myeloma controls, using an electrochemiluminescence immunoassay.
patients at first relapse who received the combination of lenalido- MVD was evaluated in trephine biopsies according to standard
mide plus dexamethasone (RD) at the standard dose, according procedures.
to their renal function. Patients were also given zoledronic acid, Results: Symptomatic MM patients had elevated PlGF (median
4 mg iv, monthly, both pre- and post-RD. Serum TIMP-1 was 19.5 pg/ml, range 6.7-91.3 pg/ml vs. 16.1 pg/ml, 10.9-25.0 pg/ml
determined on day 1/cycle 1 and on day 28/cycle 3 of RD, using of control group; p<0.01) and elevated VEGFR-1 levels (88.6 pg/
an ELISA methodology (Oncogene Science, Cambridge, MA, USA) ml, 51.5-320 pg/ml vs. 73.3 pg/ml, 62.9-100.8 pg/ml; p<0.001). In
along with serum markers of bone remodeling (CTX, TRACP-5b, MM patients there was a positive correlation between PlGF and
bALP and osteocalcin) and osteoblast/osteoclast regulators VEGFR-1 (r=0.62, p=0.009 for asymptomatic and r=0.36, p=0.01
(Dkk-1, sRANKL and OPG). for symptomatic MM). Eighteen (37%) patients with symptomatic
Results: The mean serum TIMP-1 level of all patients was 251.1 MM had low grade, while 20 (41%) had intermediate and 10
ng/ml (SD 95.4 ng/ml). Only two patients (1M/1F; 5%) had el- (20%) high grade angiogenesis. The median values and ranges of
evated values of TIMP-1 (UNL 459 ng/ml for males and 374 ng/ VEGFR-1 for low, intermediate and high grade angiogenesis were:
ml for women). Patients had increased levels of Dkk-1, sRANKL, 75.1 pg/ml (51.5-109.1 pg/ml), 94.2 pg/ml (61.2-143.8 pg/ml) and
sRANKL/OPG ratio and bone resorption markers (CTX, and TRACP- 151.8 pg/ml (103.7-320.0 pg/ml), respectively (p-ANOVA<0.0001).
5b) (p<0.01 compared with 25 healthy controls). Serum TIMP-1 These patients received frontline therapy with novel agent-based
correlated with OPG (r=0.644, p<0.001), creatinine (r=0.572, regimens: 25 with lenalidomide-, 16 with thalidomide- and 7
p<0.001), beta2-microglobulin (r=0.481, p=0.003), TRACP-5b with bortezomib-based regimens. The median follow-up period
(r=0.449, p=0.006) and Dkk-1 (r=0.444, p=0.007). Patients with was 18.8 months and 8/47 patients have died. The probability of
ISS-3 disease at diagnosis continued to have higher levels of survival was 86% at 1 year and 78% at 2 years. In the univariate
TIMP-1 at first relapse compared with those with ISS-1 or ISS-2. analysis the VEGFR-1 as a continuous variable correlated with
No significant alterations of TIMP-1 were observed after 3 cycles higher risk of death (HR: 1.011, 95% CI: 1.004-1.018, p=0.003)
of RD. TIMP-1 did not predict for survival, both as continuous Conclusion: Our study suggests that myeloma patients have
increased circulating PlGF and VEGFR-1. High VEGFR-1 correlated P41

with increased angiogenesis and inferior survival, supporting a
significant role of VEGFR-1 in the biology of angiogenesis in MM. DEVELOPMENT OF DOUBLE EXPRESSING DIFFUSE
LARGE B-CELL LYMPHOMAS IN THE COURSE OF
MULTIPLE MYELOMA, SUCCESSFULLY TREATED WITH
P40 RITUXIMAB AND LENALIDOMIDE
Paraskevi PAPAIOANNOU, Tatiana TZENOU,
OSTEOPROTEGERIN IS A SIGNIFICANT PROGNOSTIC
Eftychia NIKOLAOU, Sotiria KOTSANTI, Anastasia POULI,
FACTOR FOR OVERALL SURVIVAL IN PATIENTS WITH
Panayiota PETSA, Maria DIMOU, Theodoros ILIAKIS,
PRIMARY SYSTEMIC AMYLOIDOSIS INDEPENDENT
Panayiotis PANAYIOTIDIS, Marie-Christine KYRTSONIS
OF THE MAYO STAGING
Maria GAVRIATOPOULOU, Efstathios KASTRITIS,
Medicine, Laikon General Hospital, Ath ens,Greece
Meletios A. DIMOPOULOS, Evangelos ELEUTHERAKIS-
PAPAIAKOVOU, Nikolaos KANELLIAS, Magdalini MIGKOU, Introduction: The coexistence of two distinct lymphoprolif-
Maria ROUSSOU, Constantinos PAMBOUCAS, erative disorders is quite rare. We herein present a 63-year-old
Savvas Th. TOUMANIDIS, Evangelos TERPOS patient with multiple myeloma who developed diffuse large B-
Department of Clinical Therapeutics, National and cell lymphoma (DLBCL) 16 years after the diagnosis of multiple
Kapodistrian University of Athens, School of Medicine, myeloma (MM).
Athens, Greece Case: In 1997 our patient presented with gradually worsening
sciatica and a monoclonal serum spike. Further tests revealed
Objective: Deregulation of bone metabolism is common in multiple osteolytic lesions, a pelvic left plasmacytoma, 15%
plasma cell dyscrasias, including multiple myeloma (MM) and plasma cells infiltration in the bone marrow biopsy, an IgAN
MGUS, but very little is known for bone remodeling in patients paraprotein while the other tests were normal. He was diagnosed
with primary systemic (AL) amyloidosis. The aim of our prospec- with IgA multiple myeloma, stage according to Durie-Salmon
tive study was to evaluate bone metabolism in newly diagnosed and ISS 2; treatment was initiated with radiotherapy followed
patients with AL amyloidosis, to compare the results with those by chemotherapy. He relapsed 10 years after, with a tongue
of patients with other plasma cell neoplasms and explore pos- plasmacytoma and minimal bone marrow plasma cell infiltra-
sible correlations with disease characteristics, including survival. tion (12%); he received bortezomib-dexamethazone, achieved
Methods: We evaluated bone remodeling indices in 102 patients complete remission and subsequently underwent autologous
with newly diagnosed AL amyloidosis, 35 healthy controls, 35 stem cells transplantation. Three years later, he complained
newly diagnosed, symptomatic MM patients and 40 MGUS of continuous and worsening epigastric pain and discomfort.
patients. An enzyme-linked immunosorbent assay (ELISA) was Ultrasound followed by MRI revealed an abdominal mass and
used for the detection of the following serum indices: i) osteo- thickening of the terminal ileum, biopsy of which established
clast regulators: soluble RANKL and osteoprotegerin (OPG); ii) the diagnosis of DLBCL of the double expressing (bcl-6, bcl-2)
bone resorption markers: CTX, NTX and TRACP-5b and iii) bone subtype. Staging examination tests revealed no other lesions,
formation markers: bone-alkaline phosphatase and osteocalcin. while the bone marrow had 65% plasma cell infiltration. R-EPOCH
Results: Bone resorption markers (CTX, NTX) and osteoclast regu- combination was started resulting in partial response. Because of
lators (sRANKL, OPG) were increased in AL patients compared to coexisting myeloma, treatment continued with the combination
controls (p<0.01) but bone formation was unaffected. Myeloma of rituximab, lenalidomide and dexamethazone. fter comple-
patients had increased bone resorption and decreased bone for- tion of 6 cycles of the above mentioned regimen, he achieved
mation compared to AL patients, while sRANKL/osteoprotegerin complete remission for both diseases and was submitted to a
ratio was markedly decreased in AL, due to elevated osteoprote- second autologous stem cell transplantation.
gerin in AL (p<0.001). Osteoprotegerin correlated with NT-proBNP Conclusion: The interest of the present case lies on both the de-
(p<0.001) and was higher in patients with cardiac involvement velopment of double expressing DLBCL in the course of MM and
(p=0.028) and advanced Mayo stage (p=0.001). OPG levels above the very good response of this especially aggressive lymphoma
the upper value of healthy controls was associated with shorter to rituximab, lenalidomide and dexamethazone treatment.
survival (34 vs. 91 months; p=0.026), while AL patients with OPG
levels in the top quartile had very short survival (12 vs. 58 months;
p=0.024). In Mayo stage-1 disease, OPG identified patients with
poor survival (12 vs. >60 months; p=0.012).
Conclusion: We conclude that increased OPG in AL is not only a
compensation to osteoclast activation, but may also reflect early
cardiac damage and may identify patients at increased risk of
death within those with earlier Mayo stage.
P42 P43
POEMS SYNDROME PRESENTING WITH INSIDIOUS THE DNA REPAR CAPACTES OF THE NTERSTRAND
DISTAL PARAPLEGIA CROSS-LNKS AND DOUBLE-STRAND BREAKS N
Fatos Dilan KOSEOGLU, Hatice Demet KPER UNAL, THE OUTCOME OF ANT-MYELOMA THERAPY - THE
Pusem PATIR, Fahri SAHIN, Guray SAYDAM SYNERGISTIC EFFECT OF DNA REPAR NHBTORS
Ege University Faculty of Medicine, Izmir, Turkey Maria GKOTZAMANIDOU1,2, Evangelos TERPOS1,
Nikhil MUNSHI2, Meletios A. DIMOPOULOS1,
Introduction: We describe a patient with POEMS on the purpose Vassilis SOULIOTIS3
of emphasising the insidious symptoms of this rare syndrome. 1
POEMS syndrome is a rare multisystemic disorder characterized Kapodistrian University of Athens, School of Medicine,
by a combination of polyneuropathy, hemangioma, hyperpig- Athens, Greece, 2Department of Medical Oncology,
mentation and hypertrichosis of the skin, variable endocrine Jerome Lipper Multiple Myeloma Center, Dana-Farber
disturbances, generalized edema, organomegaly and a plasma Cancer Institute, Harvard Medical School, Boston, MA,
cell dyscrasia with an M-protein often associated with myeloma. USA, 3Institute of Biology, Medicinal Chemistry and
Patients are often misdiagnosed with myeloma or monoclonal Biotechnology, National Hellenic Research Foundation,
gammopathy of undetermined significance (MGUS). Athens, Greece
Case: A 40-year-old woman presented to the clinic of neurology
with numbness in her feet which has been occured for months. Objective: Many important anticancer agents exert their antitu-
On detailed history she has no chronic illness and drug utilization. mor effect through the production of DNA interstrand cross-links
Peripheral neuropathy had been diagnosed with electromyog- (ICLs). Herein, using the ICL-inducing drug melphalan, we inves-
raphy. Muscle power was grade three in bilateral legs. Lower tigated the underlying mechanisms in processing and repair of
limb reflexes were abnormal. No other finding was found with drug-induced DNA damage and their contribution to response
detailed physical examination. In a couple days, patient developed of Multiple Myeloma (MM) patients to anti-myeloma therapy.
bilateral foot drop, paraesthesia of her feet. Thoracolomber MRI Methods: We examined the melphalan-induced DNA damage
was performed due to her back pain. MRI showed a destructive formation/repair in MM cell lines [melphalan-sensitive (RPMI8226)
sclerotic lesion on the level of T11. An enlarged spleen (17 cm) and melphalanresistant (LR5)] and CD138+ bone marrow
and hemangioma (8 mm) in the liver was also evident on abdomi- plasma cells (BMPCs) from MM patients (8M/7F; median age 61
nal ultrasonography. Primarily, metastatic lesions secondary to years), responders (n=9) or non-responders (n=6) to subsequent
a solide tumour was considered. After detailed body scanning melphalan therapy.
with radiologic and physical examination, no suspicious focus Results: Following ex vivo melphalan treatment of BMPCs, higher
was found. Endocrinologic examination revealed hypothyroidism accumulation of monoadducts was observed in responders, due
and three hypoechoic thyroid nodules. Urine was negative for to the slower first-phase repair capacity of these cells (P<0.01).
BenceJones protein. Serum immunofixation was consistent with Although the ICL repair efficiencies were similar in all patients, ac-
immunoglobulin G monoclonal gammopathy. The lesion was cumulation of ICLs was significantly higher in responders BMPCs
biopsied under CT guidance and found to be a plasmacytoma, (P<0.01), due to higher levels of monoadducts (precursors of ICLs)
chain restricted. The presence of lytic lesions, splenomegaly, left unrepaired in these cells. Moreover, double strand breaks
hypothyroidism, hemangioma and peripheral neuropathy the (DSBs) burden was significantly higher in responders, due to
patient diagnosed with POEMS syndrome. higher accumulation of ICLs (precursors of DSBs) and lower rates
Conclusion: POEMS syndrome is a rare multisystem syndrome of DSB repair in these cells (P<0.05). An inverse correlation was
associated with plasma cell dyscrasia and can reliably be distin- found between the apoptotic rate and the DSBs repair efficiency
guished from other diseases if a thorough history is taken and of BMPCs, with the apoptotic rate being significantly higher in
examination performed. responders compared to non-responders (P<0.01). In line with
BMPCs data, significantly higher accumulation of monoadducts,
ICLs and DSBs were found in RPMI8226 compared to LR5 cells
(P<0.001). Interestingly, in all cell types analyzed, co-treatment
with DSB repair inhibitors (NU7026, IR-1) significantly increased
the accumulation of DSBs and the melphalan sensitivity of the
cells (P<0.01).
Conclusion: BMPCs from responders to melphalan treatment
are characterized by the simultaneous accumulation of the
extremely cytotoxic ICL and DSBs lesions. Moreover, our results
suggest that DSB repair inhibitors offer a strategy toward the
improvement of existing regimens in MM.
was observed in one patient along with CALR mutation. DNMT3a

MYELOPROLIFERATIVE NEOPLASMS mutations detected in 5 cases; in three along with JAK2V617F,
in one with CALR and one alone.
P44 Conclusion: Our findings indicate that HRMA-PCR represent a
A RAPID AND SENSITIVE METHOD TO DETECT rapid and sensitive method for the detection of mutations in
COMBINATIONAL MUTATIONS IN EPIGENETIC epigenetic modifiers genes. Our results suggest that routine
MODIFIER GENES IN PATIENTS WITH MYELOFIBROSIS screening for these mutations may be useful to determine a
Andreas GIANNOPOULOS1, Christine ZOI1, patients risk for thrombosis, leukaemic transformation, and
Theodoros LOUPIS1, Marina MANTZOURANI2, survival according to the bibliography.
Nora-Athina VYNIOU2, Panagiotis TSIRIGOTIS3,
Dimitris LOUKOPOULOS1, Marianna POLITOU4,
Kostas KONSTANTOPOULOS5, Katerina ZOI1 P45
1
Hematology Research Laboratory, Biomedical Research HEMATOLOGICAL COMPLETE REMISSION BY
Foundation, Academy of Athens, Athens, Greece, PONATINIB IN A CHRONIC MYELOID LEUKEMIA
2
First Department of Internal Medicine, National and PATIENT WITHOUT T315I MUTATION
Kapodistrian University of Athens, School of Medicine, idem DNKAL1, Psem PATIR2, Nur AKAD SOYER2,
Laikon General Hospital, Athens, Greece, 3Hematology Gray SAYDAM2
Unit, Second Department of Propedeutic Medicine, 1
Ege University, Department of Internal Medicine, Izmir,
National and Kapodistrian University of Athens, School
Turkey, 2Ege University, Department of Hematology, Izmir,
of Medicine, Attikon University Hospital, Athens, Greece,
Turkey
4
Laboratory of Hematology and Blood Transfusion
Unit, National and Kapodistrian University of Athens, Introduction: Imatinib was the first TKI developed to target
School of Medicine, Aretaieion Hospital, Athens, Greece, the bcr-abl protein for the treatment of chronic myeloid leu-
5
Department of Hematology, National and Kapodistrian kemia (CML), and it was followed subsequently by nilotinib,
University of Athens, School of Medicine, Laikon General bosutinib, dasatinib, and most recently, ponatinib. Ponatinib is
Hospital, Athens, Greece a third-generation TKI that is uniquely effective in inhibiting the
gatekeeper T315I mutation that confers resistance to all other
Objective: The mutational spectrum in myelofibrosis includes
driver mutations in genes such as JAK2, CALR, and MPL with kinase inhibitors.
approximate frequencies 60%, 23%, and 5% respectively. Recur- Case: A 53-year-old male presented to hematology outpatient
rent mutations in epigenetic modifiers such as ASXL1, IDH1/2 clinic with complaints of leukocytosis, in August 2009. Cytoge-
and DNMT3a have also been described. Recent studies indicate netic and PCR analyses showed the presence of Philadelphia
that the number and type of mutations have important clinical chromosome. Imatinib mesylate 400 mg/day was started. In June
consequences. In this report we describe a rapid and sensitive 2013, BCR/ABL level was found 22.55% IS. Imatinib mesylate was
HRM analysis PCR method using the LightCycler4800 for the discontinued due to loss of molecular response. Treatment was
detection of ASXL1, IDH1/2 and DNMT3a mutations. continued with dasatinib. In April 2014, BCR/ABL level was found
Methods: 119 patients with myelofibrosis were studied. DNA was 304,598% IS. In this time Dasatinib was interrupted and Nilotinib
extracted from peripheral blood samples by standard procedures. was started. In November 2014, again on the fact that loss of
JAK2V617F and MPLW515L/K mutations were detected using hematologic response, patient was evaluated refractory against
standard PCR assays (sensitivity>1%). CALR exon 9 mutations second-line tyrosine-kinase inhibitors. A molecular study did not
were detected using an HRMA-PCR assay (sensitivity>2.5%). reveal a T315I mutation of the BCR-ABL gene. It was decided to
Mutations in ASXL1, IDH1/2 and DNMT3a genes were detected start and continue ponatinib 45mg daily until an unrelated donor
using HRMA-PCR methods for the respective amplicons accord- was found for stem cell transplantation. In follow-up, ponatinib
ing to the COSMIC database. Results were confirmed by Sanger related toxicity was not observed except constipation. Four
sequencing. months later, he re-achieved hematologic response.
Results: 65 of the 119 patients carried the JAK2V617F mutation Conclusion: Conclusion Ponatinib is a potent TKI that can over-
(54.62%), 6 presented MPL mutations (5.04%), and 24 CALR muta- come several resistance mechanisms is previously treated patients
tions (20.16%). ASXL1 mutations detected in 45 patients (37.81%). with CML. Unlike other BCR-ABL TKIs, ponatinib was designed
In 25 cases ASXL1 mutations coexisted with JAK2V617F, in 6 with to overcome the T315I mutation. This case report showing the
CALR mutations, in 3 with MPL, while in 10 cases ASXL1 muta- effectiveness of ponatinib therapy for refractory against first
tions was the only molecular lesion. IDH2 mutations detected and second-line CML patients not bearing the T315I BCR-ABL
in 2 cases; in one patient coexisted with JAK2V617F and ASXL1 mutation. Further studies are necessary to confirm the efficacy
mutation, while in the other only with ASXL1. The IDH1 mutation and applicability of ponatinib therapy.
P46 of myelofibrosis and the need to start cytoreductive treatment.

10-year EFS was for patients with platelet counts <600 x 109 pcm
INCREASED PLATELET COUNTS AT DISEASE DIAGNOSIS 89%, for platelet counts between 600-800 x 109 pcm 66% and for
ARE RELATED WITH EARLY INTRODUCTION OF platelet counts >800 x 109 pcm was 22% (p=0.003, Kaplan-Mayer,
CYTOREDUCTIVE TREATMENT AND REDUCED EVENT- LogRANK test). On the contrary the presence of grade-I fibrosis
FREE SURVIVAL IN YOUNG ADULT PATIENTS WITH was not associated with reduced EFS.
ESSENTIAL THROMBOCYTHEMIA; A FOLLOW UP Conclusion: In young ET patients increased platelet counts at
STUDY OF 33 PATIENTS disease diagnosis can predict an eventful disease journey with
Emmanouil SPANOUDAKIS, Costas ZAGORIDIS, early need for the use of cytoreductive treatment and reduced EFS.
Stamatia GULIAMTZI, Dimitrios MARGARITIS,
Ioannis KOTSIANIDIS
Department of Hematology, Democritus University of P47
Thrace, Medical School, Alexandroupolis, Greece MULTICENTER-RETROSPECTIVE ANALYSIS OF TURKISH
PATIENTS WITH CHRONIC MYELOPROLIFERATIVE
Objective: Essental thrombocythemia (ET) is not such an in-
NEOPLASMS
nocent disease in young adults. Most thrombotic events occur
during diagnosis and almost half of the initially asymptomatic Nur SOYER1, Ibrahim C. HAZNEDAROGLU2,
patients will have an event during the course of their disease. Demet CEKDEMIR3, Mehmet YILMAZ4, Ali UNAL5,
Methods: Herein, we analyzed retrospectively the medical records Oktay BLGR6, Osman ILHAN7, Fusun OZDEMIRKIRAN8,
of 33 ET patients diagnosed below the age of 45 years and fol- Fahri AHN1, Guray SAYDAM1
lowed in a single institution from 1992 to 2014. Management was 1
Ege University Medical Faculty Hospital, Department
left at the discretion of the treating physician but antithrombotic of Hematology, Izmir, Turkey, 2Hacettepe University
agents were used from disease diagnosis in all patients. Among Medical Faculty Hospital, Department of Hematology,
33 young adult patients, 11 were males and 22 females. Eighteen Ankara, Turkey, 3Sakarya Research and Training Hospital,
patients were followed for a median period of 94.5 (range 45-178) Departmenta of Hematology, Sakarya, Turkey, 4Gaziantep
months and left untreated and they were included in group A. University Medical Faculty Hospital, Department of
While cytoreductive treatment was introduced in 15 patients Hematology, Gaziantep, Turkey, 5Erciyes University
included in group B. Among 15 treated patients cytoreduction Medical Faculty Hospital, Department of Hematology,
was introduced from disease diagnosis in seven patients and in Kayseri, Turkey, 6Bozyaka Research and Training Hospital,
eight during the course of their disease after a median period Department of Hematology, Izmir, Turkey, 7Ankara
on observation of 36 months (range: 6-168). University Medical Faculty Hospital, Department of
Results: We separated our patients into two groups according Hematology, Ankara, Turkey, 8Izmir Ataturk Research and
to the need to start any cytoreductive treatment and try to Training Hospital, Department of Hematology, zmir, Turkey
discover patients characteristics at diagnosis that can predict
the early use of cytoreductive treatment. Splenomegaly of any Objective: Chronic Myeloproliferative neoplasms (CMPN) that are
grade was palpated in 3/18 (16.5%) patients in group A and in Philadelphia-negative malignancies include Polycythemia Vera
2/15 (13%) in group B; p=0.796. Although hematocrit levels were (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis
equal between the two groups [42.7% (34.7-47.6) in group A and (PMF), according to WHO classification. The aim of this report was
40.7% (37.3-46) in group B; p=0.84] as were also and the leucocyte to determine the demographic features, disease characteristics,
counts [7.85 (5.6-13,2) x 103 pcm in group A and 9.73 (4.7-11.7) JAK mutational status, treatment strategies, and survival rates of
x 103 in group B; p=0.6], the median values of platelet counts at 708 patients with CMPN from 8 centers in Turkey.
diagnosis was significantly higher in group B compared to group Methods: Across all of Turkey, 8 centers were enrolled in the study.
A [805 (490-2300) x 109 pcm versus 604.5 (490-921) x 109 pcm; We retrospectively evaluated 708 patients results with CMPN.
p=0.012]. Fibrosis (grade I) at the initially performed bone mar- Results: The JAK2V617F mutation was found positive in 75.11%
row biopsy was met at higher percentages in patients allocated of patients with PV, in 51.5% of patients with ET and in 50.4% of
in group B 40% (6/15) in group B and 11% (2/18) at group A; patients with PMF. Thrombosis occurred in 20.65% of patients
p=0.03. JAK2V617F was detected in 40% (6/15) in group B and with PV, in 15.12% of patients with ET and in 9.6% of patients
50% (9/18) in group A; p=1. According to the IPSET-thrombosis with PMF. Bleeding at diagnosis occurred in 7.5% of PV patients,
scoring system in group A most patients had low thrombotic in 9% of ET patients and in 10.4% of PMF patients. Six hundred
risk 10/18, 7/18 had intermediate thrombotic risk and 1/18 had and eight patients (85.9%) had a cytoreductive therapy. The most
high thrombotic risk. In group B 7/15 had low thrombotic risk, common used drug was hydroxyurea (75.1%). Cytoreductive
3/15 intermediate and 5/15 had high thrombotic risk. In the total therapy was changed in 198 (28% of all) patients. In the second-
cohort of 33 young ET patients platelet counts at disease diagnosis line treatment, the most common used drug was anagrelide (147
can predict reduced event free survival (EFS). As an event were of 198 patients). Anti-platelet therapy was used in 553 (78.1%)
considered thrombohemorhagic complications, development patients. Splenectomy was performed in 10 (1.4%) patients.
Eight PMF patients (1.1% of all CMPN patients) were treated

with allogeneic stem cell transplantation. Progression to acute TRANSPLANTATION AND GENE
leukemia and secondary myelofibrosis were observed in 0.6 % THERAPY
and 11.3% of all patients, respectively. The median follow- up
was 38 months (0-322) and overall survival (OS) was 86.7% at P49
10 years in all patients.
Conclusion: Our patients results is compatible the literature LOW CIRCULATING MANNAN-BINDING LEPTIN
except the frequency of JAK2V617F mutation in PV patients. LEVELS CORRELATE WITH INCREASED NUMBER
Hydroxyurea was the most common used cytoreductive therapy OF FEBRILE EPISODES IN MYELOMA PATIENTS
in our patient cohort. WHO UNDERGO AUTOLOGOUS STEM CELL
TRANSPLANTATION AND DO NOT RECEIVE
ANTIBIOTIC PROPHYLAXIS
P48 Evangelos ELEUTHERAKIS-PAPAIAKOVOU,
Evangelos TERPOS, Dimitrios CHRISTOULAS,
A CASE OF COLON ADENOCARCINOMA IN A PATIENT
Magdalini MIGKOU, Maria GAVRIATOPOULOU,
WITH CHRONIC MYELOID LEUKEMIA TREATED WITH
Maria GKOTZAMANIDOU, Ioannis PANAGIOTIDIS,
DASATINIB
Efstathios KASTRITIS, Meletios A. DIMOPOULOS,
Psem PATIR1,Damla GNEN2, Damla AKDA3, Christos PAPADIMITRIOU
Fahri AHN1, Gray SAYDAM1
1
Ege University, Department of Hematology, zmir, Turkey, Kapodistrian University of Athens, School of Medicine,
2
Ege University, Department of Internal Medicine, zmir, Athens, Greece
Turkey, 3Ege University, Department of Infectious Diseases
and Microbiology, zmir, Turkey Objective: Patients with multiple myeloma (MM) are at a higher
risk of infections. The mannan binding leptin (MBL) pathway of
Introduction: Chronic myeloid leukemia (CML) is a chronic the complement system is part of the innate immune system and
myeloproliferative disorder, caused by the unregulated prolif- seems to influence the risk of infections in cancer patients dur-
eration of granulocytes at different stages of development and ing treatment. The aim of this study was to evaluate the impact
maturation. Solid tumors may occur in 3% of the patients with of MBL levels on the risk of infections and of febrile episodes in
CML. Especially, in older ages, a second malignancy is much MM patients who undergo autologous transplantation (ASCT).
more common. Methods: We studied 100 MM patients who underwent an
Case: We report the case of a 54-year-old woman carrier Ph+ ASCT between 1996-2011. Sixty-seven patients participated in
CML who developed colon adenocarcinoma under the therapy a randomized study, where in the A arm patients received pro-
of dasatinib that was started after five years of imatinib therapy phylactic antibiotics during ASCT, while in the arm B there was
that was discontinued due to loss of molecular response. Dur- no antibiotic prophylaxis. MBL serum levels were measured in all
ing treatment with oxaliplatin-capecitabine and dasatinib, CML patients on the day of mobilization, using an ELISA methodology
relapse and serious myelosuppression were not observed. (R&D Systems, Minneapolis, MN, USA).
Conclusion: Our report suggests that the clinician should carefully Results: Seventeen patients had MBL levels <500 mg/L (the lower
check the CML patients, especially elder, in terms of secondary normal limit). Of those, 11 received antibiotics prophylaxis and 6
malignacy on routine follow-up and dasatinib is an important did not. In general, there was no statistical difference regarding
treatment option for colon adenocarcinoma cancer in patients the development of fever or neutropenic fever between patients
with CML. with MBL serum levels of <500 mg/L or >500 mg/L. However,
among 17 patients with MBL levels of <500 mg/L, 6/11 patients
who received antibiotics prophylaxis developed a febrile episode
compared to 6/6 patients who did not receive antibiotics prophy-
laxis and developed a febrile episode (p=0.049). Nevertheless,
patients with MBL levels <500 mg/L attained a lower response
rate to first line therapy with antibiotics, requiring administra-
tion of a second line regimen, compared to patients with MBL
levels of >500 mg/L (66.7% versus 88.9%, respectively; p=0.05).
Conclusion: MM patients who undergo ASCT and have low
MBL levels have a lower response rate in first line antibiotic
regimens, requiring more often administration of a second, more
advanced, line of antibiotics. The administration of prophylactic
antibiotics to these patients seems to reduce the number of
febrile episodes.
P50 for longer TTP in patients achieving sCR compared to others (48
vs. 35 months, p=0.145).
EFFICACY AND SAFETY OF BORTEZOMIB Conclusion: Four cycles of VR consolidation without dexa-
AND LENALIDOMIDE CONSOLIDATION POST- methasone is an effective regimen which improves the quality
AUTOLOGOUS STEM CELL TRANSPLANTATION of response in approximately 40% of patients and produces long
IN PATIENTS WITH MULTIPLE MYELOMA: FINAL TTP. In the absence of bisphosphonates, VR consolidation has
RESULTS OF A PROSPECTIVE STUDY beneficial effects on bone metabolism and is related with no SREs.
Evangelos TERPOS, Efstathios KASTRITIS,
Dimitrios CHRISTOULAS, Evangelos ELEUTHERAKIS-
PAPAIAKOVOU, Maria GAVRIATOPOULOU, P51
Magdalini MIGKOU, Despoina KALAPANIDA,
SUCCESSFUL MOBILIZATION WITH PLERIXAFOR,
Maria ROUSSOU, Flora ZAGOURI,
USED AS SALVAGE REGIMEN AFTER CHEMO-
Meletios A. DIMOPOULOS
MOBILIZATION, FOR PATIENTS WITH MULTIPLE
Department of Clinical Therapeutics, National and MYELOMA WHO RECEIVED RADIOTHERAPY PRIOR
Kapodistrian University of Athens, School of Medicine, TO AUTOLOGOUS TRANSPLANTATION
Athens, Greece
Objective: The primary endpoint of the study was to explore Dimitrios ZIOGAS, Ioannis PANAGIOTIDIS,
the efficacy of VR (bortezomib and lenalidomide) consolidation, Magdalini MIGKOU, Despoina FOTIOU,
without dexamethasone, in newly-diagnosed patients with Christine LIACOS, Efstathios MANIOS,
multiple myeloma (MM), who received bortezomib-based induc- Efstathios KASTRITIS, Meletios A. DIMOPOULOS,
tion treatment and then underwent autologous transplantation Evangelos TERPOS
(ASCT). Secondary endpoints included: safety, time to progression Department of Clinical Therapeutics, National and
(TTP), time to next treatment (TtNT), overall survival (OS) and VR Kapodistrian University of Athens, School of Medicine,
effects on bone metabolism in the absence of bisphosphonates Athens, Greece
administration.
Methods: Between January 2010 and November 2013, 59 patients Objective: High dose melphalan (HDM) and autologous stem
(30M/29F, median age 54 year) who achieved at least stable cell transplantation (ASCT) remains the treatment of choice for
disease post-ASCT were entered into this study. Consolidation eligible patients with multiple myeloma (MM). Prior adminis-
consisted of 4 VR cycles, which started on day 100 post-ASCT. tration of radiotherapy before ASCT has been associated with
Bortezomib was given at a dose of 1.3 mg/m2, on days 1, 4, 8 poor stem cell mobilization. We report two MM patients who
and 11 of a 21-day cycle, while lenalidomide was given at a dose underwent extensive radiotherapy prior to ASCT and required
of 25 mg, p.o., daily on days 1-14. Patients did not receive any plerixafor administration as salvage mobilization agent, after
bisphosphonate during the study. We measured the following chemo-mobilization with cyclophosphamide and G-CSF.
bone remodeling molecules on the day of stem cell collection Methods: The first patient (a 42-year-old male) received ra-
and then before and after VR consolidation: sRANKL, osteopro- diotherapy (30Gy) in right costal arch for plasmacytoma and
tegerin, dickkopf-1, sclerostin, CTX, TRACP-5b, bone-specific additional radiotherapy (30Gy) in T6-T9 vertebrae for T8 plasma-
ALP and osteocalcin. cytoma. Patients therapeutic regimen also included 3 cycles of
Results: Before HDM, one (1.7%) patient had achieved a sCR, PAD. Due to residual disease he received 3 additional PAD cycles.
one (1.7%) CR, 30 (50.8%) vgPR, 22 (37.3%) PR, while 5 (8.5%) The second patient (a 52-year-old man) received radiotherapy
patients had stable disease. After ASCT, 34 (57.6%) patients (30Gy) on thoracic vertebrae due to plasmacytoma evolving
improved their status of response, while after VR consolidation, from T2 vertebra. He also received 4 cycles of anti-myeloma
23/59 (39%) patients further improved their response status. therapy with VCD.
Overall, 30 (50.8%) patients achieved a sCR, one (1.7%) CR, 26 Results: The first patient received chemo-mobilization with 2.5
(44.1%) vgPR and two (3.4%) PR. The most important adverse g/m2 cyclophosphamide and G-CSF. Initial stem cell harvested
events included neutropenia (68%, grade 3/4 23%), thrombo- 0.8x10^6 CD34+/kg. Salvage administration of plerixafor on the
cytopenia (59%, 7%), peripheral neuropathy (56%, 2%), anemia night of first collection date resulted in a subsequent harvest of
(50%, 4.5%), skin rash (34%, 9%), infections (34%, 0%), fatigue 6.2x10^6 CD34/kg. The latter collection allowed HDM administra-
(20%, 0%), diarrhea (16%, 0%) and constipation (14%, 2%). No tion and stem cell re-infusion. The second patient received stem
patient developed deep vein thrombosis. Post-VR consolidation cell mobilization with 2.5 g/m2 cyclophosphamide and G-CSF.
there was a reduction of sRANKL/OPG ratio and of sclerostin Initial harvest resulted in collection of 1.2x10^6 CD34+ cells/kg.
(p<0.001), while no skeletal-related events (SREs) were observed Plerixafor was administered and led to a second collection of
during the study period. The median follow-up after the ASCT 8.6x10^6 CD34+/kg that allowed administration of HDM.
was 35 months (range: 7-60) and 24 patients have progressed. Conclusion: Plerixafor has been reported to increase 4-5 times the
The median TTP after the ASCT was 42 months. There was a trend number of collected stem cells when it is used as initial mobiliza-
tion regimen with G-CSF or 2-3 times when it is used as salvage After culture under GMP conditions, mononuclear cell rate was
regimen after chemo-mobilization with cyclophosphamide found to be 24% on hours 96 and 120. It was seen that 88% of
and G-CSF. Our cases support that plerixafor facilitates stem cell mononuclear cells transformed to mature dendritic cells after
mobilization (>7 fold compared to chemo-mobilization) in MM 96-hours culture.
poor mobilizers after radiotherapy. Further data are needed to Conclusion: In cancer patients, tumor vaccine obtained from
clarify this issue and to determine the best mobilization regimen allogeneic sibling donor can be used in lieu of autologous tumor
for this subgroup of patients. vaccine and it is thought to be more effective. In cancer patients,
minimal residual disease can be eliminated by active tumor
vaccine after reducing tumor burden by standard methods.
P52 Allogeneic dendritic cells produced at 37C in CO2 media under
GMP conditions can be used in tumor immunotherapy. More
THERAPEUTIC CANCER VACCINE: PRODUCING
effective method would have been used by employing dendritic
DENDRITIC CELL FROM ALLOGENEIC DONOR STEM
cells against cancer stem cells rather than cancer cells itself.
CELLS
Aye BREKUL,Ali NAL, Esen KARAKU,
Mehmet ar NAL, Yusuf ZKUL, Yavuz KKER P53
Erciyes University, Department of Hematology, Kayseri, Turkey
SAFETY AND EFFICACY OF CHEMO-MOBILIZATION
Objective: Tumor immunotherapy is a treatment modality that AND LARGE VOLUME LEUKAPHERESIS IN
has been long attempted to use as a supportive treatment along HEMATOLOGY/ONCOLOGY PATIENTS: A SINGLE
with standard therapies. Cellular therapy, a method of tumor im- CENTER EXPERIENCE IN 327 PATIENTS
munotherapy, is introduced in cancer therapy as allogeneic and Evangelos ELEUTHERAKIS-PAPAIAKOVOU,
autologous stem cell transplantation. Donor leukocyte infusion Magdalini MIGKOU, Ioannis PANAGIOTIDIS,
is a salvage method to regain remission in patients with recur- Christine LIACOS, Maria ROUSSOU, Efstathios
rent or minimal residual disease after stem cell transplantation. MANIOS, Efstathios KASTRITIS, Evangelos TERPOS,
T lymphocytes and antigen-presenting cells (dendritic cells) Christos PAPADIMITRIOU, Meletios A. DIMOPOULOS
are two cell lineages that play crucial role in the battle of organ- Department of Clinical Therapeutics, National and
ism against cancer. Close similarity between cancer cells and Kapodistrian University of Athens, School of Medicine,
normal cell structure is the most important reason of escape Athens, Greece
from defense cells, namely T lymphocytes. Stimulation and
enhancement of T lymphocytes against cancer cells comprise Objective: Autologous stem cell transplantation (ASCT) is widely
principal part of therapy. Tumor immunotherapy involves active used for the management of lymphomas and myeloma. To im-
immunotherapy, passive vaccination and immunomodulatory prove stem cell (SC) collection efficiency, chemo-mobilization
therapies. Active immunotherapy provides better recognition of combined with large volume leukapheresis has been evaluated
tumor-related antigens by immune system of patient, enhanced as a more efficient apheresis procedure. Here we report our
immune system and elimination of malignant cells. This modal- experience regarding the safety and efficacy of large volume
ity employs therapeutic potential of donor specific and tumor leukapheresis.
specific immune responses. Active immunotherapy targets im- Methods: Between 1996-2010, 327 patients with hematological
munosuppressive and tolerogenic mechanisms suppressed by malignancies or solid tumors have been recruited in our study.
tumor. Active immunotherapy has emerged in clinical practice The vast majority of patients received intravenous cyclophos-
since 1990 following years of experimental studies. phamide (4 mg/m2 or 2.5 mg/m2) with G-CSF for mobilization
Methods: To generate allogeneic dendritic cells, leukemic stem of peripheral blood SC (PBSC). PBSC collection was performed
cells were isolated from blood samples drawn from patients with with a COBE Spectra Blood Cell Separator (COBE Laboratories,
acute leukemia. Lysate was prepared from leukemic stem cells Lakewood, CO). Large volume leukapheresis was defined either
identified by flow cytometry. For allogeneic stem cell transplan- by processing a minimum of 15L of peripheral blood or by pro-
tation, stem cells and mononuclear cells (1x10 >6/kg) obtained cessing more than three times the total peripheral blood volume,
from sibling donors by apheresis were separated to produce as previously reported.
tumor vaccine. For dendritic cell transformation, GM-CSF and Results: 327 patients underwent a cumulative total of 407 SC
IL-4 were added to media where leukemic stem cell lysate from collections. Large volume leukapheresis was generally well toler-
patient and mononuclear cells from sibling donor were treated. ated with hypocalcaemia, decrease in platelets counts (median
Surface markers for dendritic cells including CD80, CD83 and decrease 46.7%) and hypokalemia being the most common side
CD86 were evaluated in samples obtained from cultured cell on effects. 90% of patients managed to collect sufficient number
the hours 48, 72 and 96 by using flow cytometry. of SC for transplantation (defined as >3106 CD34/kg) whereas
Results: Mononuclear cells were detected by 27% among almost of these patients (67%) managed to collect sufficient SC
logeneic hematopoietic cell groups harvested by apheresis. with one harvest and 46 (16%) patients yielded enough cells to
allow a second transplantation. The median product volume per (min: 10, max: 13) days, and mean platelet engraftment period
collection was 350 ml (range 50-838 ml). The median total CD34+ was 13.2 3.02 (min: 10, max: 23)days. Five of the patients are
cell yield/kg was 6.46106 CD34+ cells/kg (0-64.7). Factors that still waiting for transplantation.
negatively affected SC yield were >2 lines of chemotherapy or Conclusion: Plerixafor addition to G-CSF is effective on mobiliza-
radiotherapy before HDT, while patients with >65kg needed more tion as well as the collection of adequate number of stem cells
often at least two days for sufficient SC collection. with drug combination in cases who have been scheduled with
Conclusion: Large volume leukapheresis in combination with autologous stem cell transplantation and from whom adequate
stem cell chemo-mobilization is a relatively safe and highly ef- number of stem cells could not have been collected with che-
ficient procedure, leading in a successful collection in the vast motherapy followed by G-CSF.
majority of patients, minimizing the use of more advanced and
more expensive mobilization regimens.
P55
EVALUATION OF PERIPHERAL BLOOD STEM CELL
P54 MOBILIZATION AND COLLECTION IN ELDERLY
EFFICIENCY OF PLERIXAFOR FOR AUTOLOGOUS PATIENTS
STEM CELL MOBILIZATION; A SINGLE CENTER Ali NAL, Mehmet ar NAL, Aye BREKUL,
EXPERIENCE FROM TURKEY Leylagl KAYNAR, Esra YILDIZHAN, Blent ESER,
Ali NAL1, Aye BREKUL1, Mehmet ar NAL1, Mustafa ETN
Glah AKYOL1, Leylagl KAYNAR1, Esra YILDIZHAN1, Erciyes University, Department of Hematology, Bone Marrow
Serdar IVGIN2, Esen KARAKU1, Blent ESER1, Transplant Center, Kayseri, Turkey
Mustafa ETN1
1
Erciyes University, Department of Hematology, Kayseri, Objective: Adequate hematopoietic stem cell mobilization
Turkey, 2Erciyes University, Department of Internal and collection is essential for patients who are candidate for
Medicine, Kayseri, Turkey autologous stem cell transplantation. In this study we compared
mobilization success rates, amount of collected stem cells and
Objective: In this study, plerixafor stem cell mobilizing activity the factors that could affect the procedure for patients younger
was assessed in patients with autologous stem cell transplanta- and older than 60 years old.
tion and the adequate number of stem cell could not have been Methods: For this study, 112 patients who admitted to Erciyes
collected with chemotherapy and G-CSF (granulocyte colony University BMT Center for autologous stem cell transplanta-
stimulating factor) before. tion were enrolled. Thirty-three of them (36%) were under 60
Methods: This study was participated by 25 patients, from whom years called young group and 76 of them (%64) over 60 years
adequate stem cell numbers could not have been collected with called elderly group. Among the participants, 73 of them were
chemotherapy and filgrastim (10 mcg/kg) at Erciyes University multiple myeloma, 23 of them Non-Hodgkins lymphoma, 17 of
Department of Hematology Apheresis Unit between 27.01.11 them Hodgkins lymphoma. Between the groups we compared
and 06.09.14. In the second-line treatment for 15 patients, sub- the amount of pre-apheresis white blood cell (WBC), platelets,
cutaneous plerixafor 0.24 mg/kg was applied, and the remaining peripheral CD34+ cells, value of collected CD34+ cells and
10 patients a couple of weeks later. The collected CD34 + cell mononuclear cells, mobilization failure and success rates and
numbers and percentage ratios were analyzed. number of apheresis sessions.
Results: Donors of 8 (32%), Multiple Myeloma, donors of 4 (16%) Results: The median values of pre-apheresis peripheral CD34+
Hodgkins lymphoma, and donors of 8 (32%) Non-Hodgkins cells were 8.72106/kg and platelets were 86109/L in young
lymphoma (follicular, B and T cell lymphomas) and donors of 5 group; CD34+ cells were 8.9510 6/kg and platelets were
of (20%) is the diagnosis of testicular tumors. Sixteen patients 86.5109/L in elderly group (p=0.918 and p=0.899, resectively).
were male(64%) and 9 were female (36%). Mobilization process The median values of collected CD34+ cells were 7.61106/kg
for 10 patients using peripheral and central venous catheter (range: 2.52-46.62) and 7.60106/kg (2.87-25.50) in under and
was used in 15 patients. The median age of donors 46 (min: over 60 years, respectively (p=0.800). Also the median values of
17, max: 71), the median weight of 67 kg (min: 50, max: 96kg). total collected mononuclear cells (MNC) were 1.41107/kg and
Mean dose of G-CSF was 10.5 2.0 (min: 6 max: 13). Before the 1.4107/kg in young and elderly group, respectively (p=0.607).
procedure, peripheral CD34 (+) cell count was median 21.85/ It was found as 1.89 days in elderly group and 1.7 days in young
microliter (min: 2.20, max: 103.80)and median collected CD34 group when we compared their apheresis sessions (p=0.786).
(+) cell count was 4X106 / kg (min: 2.35, max: 13.58). Five of our There was no statistical significance between two groups; de-
patients could not be gathered enough stem cells. Autologous spite the mobilization failure rates were 18% and 6% in patients
stem cell transplantation was performed to 17 of all patients older and younger than 60 years (p=0.087). On the other hand,
that adequate number of stem cells has been collected. Average the number of multiple myeloma in the patients with applied
neutrophil engraftment period of these patients was 10.6 0.89 autologous stem cell mobilization was higher in elderly patients
than young ones (p=0.004) and we also demonstrated that the of CD34+ cells in the final leukapheresis product, total yield of
failure of mobilization were lower in patients with multiple CD34+ cells, and product volume data were comparable for both
myeloma than lymphoma patients (p=0.003). There was no devices (0.74% versus 0.97% CD34+, p=0.103; 6.85 versus 7.1 x
significant difference between the amounts of pre-apheresis 106 CD34+/kg, p=0.752; and 403.5 versus 353 ml graft volume,
WBC, platelets and peripheral CD34+ cells in mobilization failure p=0.094, respectively). Time to engraftment was also compa-
group and success group. rable for both apheresis devices. More specifically, time interval
Conclusion: We demonstrated that the amount of pre-apheresis to neutrophil counts >500/l, neutrophil counts >1500/l did
peripheral or collected CD34+ cells and numbers of apheresis not significantly differ (10 days versus 9 days, p= 0.386 and 11
sessions are not significantly different in comparison of the days versus 10 days, p=0.229, respectively). However a delay in
young and elderly patients who are planned autologous stem platelet recovery with Optia device need to be confirmed with
cells transplantation. Mobilization failure rate was higher in additional data from apheresis procedures (median time to
lymphoma patients than myeloma patients. It was also found platelet counts >25000/l was 12 days versus 11 days for COBE
that mobilization failure rates were higher in elderly patients Spectra, respectively; p=0.037). Platelet loss with Optia was less
than young patients. than with COBE Spectra (1278 versus 2415103/l, p=0.014). No
significant differences were observed for product hematocrit
between Optia and COBE Spectra (5.7% versus 6.6%, p=0.392).
P56 Conclusion: The automatic Spectra Optia aphereses were as-
sociated with similar and equally variable stem cell collections
MOBILIZATION OF AUTOLOGOUS PERIPHERAL as aphereses with COBE Spectra. Further data are needed to
BLOOD STEM CELLS WITH SPECTRA OPTIA V5.0: A clarify the potential benefit of lower platelet loss using Optia.
SINGLE CENTER EXPERIENCE WITH AN AUTOMATIC We continue to use this procedure in our center and updated
INTERFACE-CONTROLLED APHERESIS SYSTEM results will be presented in the meeting.
Ioannis PANAGIOTIDIS, Magdalini MIGKOU,
Dimitrios ZIOGAS, Despoina FOTIOU, P57
Christine LIACOS, Despoina KALAPANIDA, TECAM (THIOTEPA, ETOPOSIDE, ARA-C,
Efstathios KASTRITIS, Evangelos TERPOS, CYCLOPHOSPHAMIDE AND MELPHALAN) AS
Meletios A. DIMOPOULOS CONDITIONING REGIMEN FOR AUTOLOGOUS STEM
Department of Clinical Therapeutics, National and CELL TRANSPLANTATION IN PATIENTS WITH NON-
Kapodistrian University of Athens, School of Medicine, HODGKIN LYMPHOMA: RETROSPECTIVE SINGLE
Athens, Greece CENTER EXPERIENCE
Pusem PATIR1, Melda CMERT ZKAN2,
Objective: Available manual apheresis systems generally pro- Damla GUNENC3, Aye Uysal ORUC1, Mustafa DURAN1,
duce stem cell yields of consistently high quality that can be Elvina ALMURADOVA3, Fahri AHN1, Gray SAYDAM1
safely used for autologous transplantation. However, manual 1
Ege University Faculty of Medicine, Department of
apheresis needs continuous interface monitoring/adjustment,
Hematology, Izmir, Turkey, 2Inonu University Faculty
suffers from interface instability in poor mobilizers, high collection
of Medicine, Department of Hematology, Malatya,
variability, high platelet loss and failure to electronically docu-
Turkey, 3Ege University Faculty of Medicine, Department of
ment parameters. A new advanced apheresis system, Spectra
Internal Medicine, Izmir, Turkey
Optia v5.0, featuring optical sensors, which provide real time
automatic interface and product line control, was designed to Objective: High-dose chemotherapy regimens for conditioning
override these disadvantages. followed by autologous stem cell transplantation (ASCT) gener-
Methods: In our study, we evaluated data of 10 stem cell leuka- ally provide favorable results in non-Hodgkin lymphoma (NHL).
phereses performed in 8 patients with various malignancies using We have evaluated the efficacy and tolerability of a high-dose
Spectra Optia after 2011 to test its feasibility and effectiveness. conditioning regimen comprising TECAM [thiotepa (40 mg/m2
We compared our data with those obtained from 225 patients x four days), etoposide (200 mg/m2 x four days), cytosar (200
that had undergone a stem cell collection for autologous trans- mg/m2 x four days), cyclophosphamide (60 mg/kg x one day),
plantation in our Department between 2004 and 2011, using and melphalan (60 mg/m2 x two days)] in patients with NHL.
the COBE Spectra machine. Methods: Seven patients (4 F, 3 M) with NHL at various stages
Results: The use and function of automatic interface control of who underwent ASCT were included in this retrospective study.
Spectra were satisfactory. Due to the application of lower inlet The median age at transplantation was 59 (range, 4768). The
volumes/min, as compared to corresponding volumes with the diagnoses were as follows: 2 diffuse large B-cell NHL, 1 angio-
COBE Spectra machine, our apheresis with Spectra Optia usually immunoblastic T-cell lymphoma, 1 marginal zone lymphoma,
took a longer time (median 447 min versus 317 min, p<0.005). 1 follicular lymphoma, 1 T-cell lymphoblastic lymphoma and 1
Regarding other collection parameters, such as the percentage mantle cell lymphoma.
Results: All patients completed the therapy protocol. The me- gram-negative bacterias. 3.7% efficient pathogen microorganism
dian of collected CD34+ cells was 7.95x106/kg (range from 3.6 was isolated from urine cultures, all of them were gram-negative
to 13.8x106/kg). Engraftment for neutrophils and platelets was bacterias. 19.4% efficient pathogen microorganism was isolated
always achieved except one patient. The median time to recovery from catheter cultures. 57.1% of pathogens were gram-positive,
of absolute neutrophil (500/L) and platelet (20,000/L) counts 42.9% were gram-negative bacterias. 1.8% efficient pathogen
independent of transfusion was from 10 to 19 days (median, 12 microorganism was isolated from sputum, all of them were gram-
days) and 1141 days (median, 25 days), respectively. The median negative bacterias. A pathogen was isolated in 8.3% of stem cell
stay in hospital was 45 days (range, 25108). Infections were well products. Serum galactomannan antigen (SGA) was detected
controlled with antibiotics and resolved after engraftment. Non- positive in 12 (11.1%) episodes and false positivity of SGA was 8.8%
infective complications resolved after neutrophil recovery. One in all HSCTs. CMV-DNA was positive in 10.2% episodes. Fifty-nine
patient died due to transplant-related complications, as septic HRCT was performed in FNEs. Pneumonia was detected 15.7%
shock with acute distress respiratory syndrome. The overall re- in all episodes. 29.4% of pneumonia that detected in HRCTs was
sponse rate was 71% (4 CR, 57%; 1 PR, 14% ), whereas 1 patient fungal and no viral pneumonia was detected.
(14%) was refractory to TECAM. Conclusion: It can supply useful additive for a better FEN man-
Conclusion: Treatment of primary progressive and refractory NHL agement process if the medical centers follow their infection
remains particularly difcult. ASCT with variety of conditioning agents closely, perform CMV and SGA assays and modify their
regimen has been stil the best option. TECAM treatment regimen empiric antibiotic treatment policies in especially HSCT groups.
provided favorable outcomes as CR in 4 out of 7 patients, with
no signicant increase in infective and noninfective complica-
tions and only 1 transplant-related deaths. Randomized trials P59
on large numbers of patients may be useful to conrm the high
AUTOLOGOUS HEMAPOIETIC STEM CELL
anti-NHL activity and low toxicity of this treatment schedule in
MOBILIZATION AND HARVEST BY AGE GROUPS IN NON
poor-prognosis NHL patients.
HODGKIN LYMPHOMA: A SINGLE CENTER EXPERIENCE
Melda CMERT ZKAN1, Cansu ATMACA MUTLU2,
P58 Fahri AHN1, Filiz VURAL1, Mahmut TB1,
Murat TOMBULOLU1, Gray SAYDAM1
EVALUATION OF FEBRILE NEUTROPENIC EPISODES 1
Ege University, School of Medicine, Department of
IN AUTOLOGOUS HEMATOPOIETIC STEM CELL
Hematology, Izmr, Turkey, 2Ege University, Chool of
TRANSPLANTATION FOR NON-HODGKIN LYMPHOMAS
Medicine, Department of Internal Medicine, Izmr, Turkey
Cansu ATMACA MUTLU1, Melda CMERT ZKAN2,
Fahri AHN2, Filiz VURAL2, Mahmut TB2, Objective: Autologous hemopoetic stem cell transplantation
Murat TOMBULOLU2, Gray SAYDAM2 (aHSCT) can offer potential long-term remission or cure in patients
1
Ege University, School of Medicine, Department of Internal with relapsed or refractory non-Hodgkin lymphoma (NHL).The
Medicine, Izmr, Turkey, 2Ege University, School of Medicine, mobilization of HSCs can be a limiting factor for transplanta-
Department of Hematology, Izmr, Turkey tion. HSCs mobilization, harvest and engraftment periods were
evaluated by age groups.
Objective: The most important cause of mortality in febrile Methods: Fifty-four relapsed/refractory NHL cases treated with
neutropenic episodes (FNEs) that mature after autologous hema- aHSCT in Ege University between 2008-2014 were evaluated
topoietic stem cell transplantations (aHSCT) is infections. Broad- retrospectively. Patients were divided into 3 groups according
spectrum empric antibiotherapy must be started immediately as to age range;first group was 18-59 years, second group 60-64
a standard approach in FNEs. Identification of infectious agents years and third group was >65 years old.
in Non-Hodgkin Lymphoma (NHL) group was aimed. Results: Group 1 was consisted of 18 patients, group 2 of 17
Methods: One hundred and eight aHSCT data from 108 relapsed/ and group 3 of 19 patients. All the patients were mobilised af-
refractory NHL patients who was underwent transplantation at ter a salvage chemotherapy regimen (ICE or ESHAP) combined
the Hospital of Ege University, Adult Hematology Department, with 10g/kg/day dose of filgrastim. Mean collection day after
Transplant Center between 2008 and 2014 were analyzed ret- filgrastim administration was 6.2 days for group 1, 5.2 for group
rospectively. 2 and 6.8 days for group 3. Mean apheresis cycle was 2.4 for
Results: Sixty-six patients were male and 42 female. The mean group 1, 2.7 for group 2 and 2.9 for group 3. Mean total CD34+
age was 53.1 years (19-76). Central venous catheter was used in HSCs number was 8.5x106 for group 1, 5.9x106 for group 2 and
88 (81.5%) HSCTs. FNEs was detected in 106 (98.1%) HSCT. All 7.4x106 for group 3. There was no statistically significnt differ-
the patients received antiviral and antifungal prophylaxis and ence between groups in terms of HSCs collection day and total
antibacterial prophylaxis was used in 53 (49.1%) HSCT. In FNEs, apheresis cycle, but CD34+ HSCs number was statistically higher
14.8% efficient pathogen microorganism was isolated from blood in group 1 compared to group 2, but interestingly there was no
cultures. 72.8% of pathogens were gram-positive, 27.2% were statistical difference between groups 1 and 3. OS after aHSCT
was 22.7 months in group 1, 20.4 in group 2 and 19.6 months in HSCs number. Mean neutrophil and platelet engraftment time
group 3. Transplantation related mortality (TRM) was 8% in group was 12.4 and 14.4 days, respectively. There was no statistically
1, 11.7% in group 2 and 20.1% in group 3 (p<0.05). difference in neutrophil and platelet engraftment time in terms of
Conclusion: High-dose chemotherapy, followed by aHSCT, sex, type of HL and radiotherapy history.Transplantation related
is an effective treatment option for patients with relapsed/ mortality was 1.7%, complete and partial remission after aHSCT
refractory NHL, but TRM is significantly higher in >65 years old was obtained in 37 (67%) and 9 (16%) of patients, respectively.
patients. Therefore, patients must be carefully selected. There Overall survival was significantly better in patients with complete
is no reason to explain the HSC quantity difference between remission (p<0.05).
the groups,because there is no statistically difference between Conclusion: High-dose chemotherapy, followed by aHSCT,is an
group 1 and 3 but HSC quantity is lower in group 2. Larger study effective treatment option for patients with relapsed/refractory
groups and different parameters are needed to demonstrate Hodgkin lyphoma, allowing further consolidation of response.
this difference.
P61
P60 COMPARISON OF AUTOLOGOUS HEMATOPOETIC
AUTOLOGOUS HEMAPOIETIC STEM CELL STEM CELL MOBILIZATION AND HARVEST DATA IN
MOBILIZATION AND HARVEST IN HODGKIN HL AND NHL PATIENTS
LYMPHOMA: A SINGLE CENTER EXPERIENCE Melda CMERT ZKAN1, Cansu ATMACA MUTLU2,
Cansu ATMACA MUTLU1, Melda CMERT ZKAN2, Fahri AHN1, Filiz VURAL1, Mahmut TB1,
Fahri AHN2, Filiz VURAL2, Mahmut TB2, Murat TOMBULOLU1, Gray SAYDAM1
Murat TOMBULOLU2, Gray SAYDAM2 1
Ege University, School of Medicine, Department of
1
Ege University, School of Medicine, Department of Internal Hematology, Izmr, Turkey, 2Ege University, School of
Medicine, Izmr, Turkey, 2Ege University, School of Medicine, Medicine, Department of Internal Medicine, Izmr, Turkey
Department of Hematology, Izmr, Turkey
Objective: Autologous Hematopoietic Stem Cell Transplantation
Objective: Hodgkin lymphoma (HL) is one of the most common (aHSCT) provides cure option for relapsed/refractory lypmhoma
malignancies in young adults and has become curable for the patients. Poor mobilization of hematopoietic stem cells (HSCs)
majority of patients with autologous hematopoetic stem cell can be a limiting factor for aHSCT. Non Hodgkin Lyphoma (NHL)
transplantation (aHSCT), even in advanced stage. The mobiliza- and Hodgkin Lypmhoma (HL) was compared in terms of HSCs
tion of hematopoietic stem cells (HSCs)can be a limiting factor mobilization, harvest and engraftment periods.
for transplantation.HSCs mobilization, harvest and engraftment Methods: Sex and age matched 55 relapsed/refractory NHL and
periods were evaluated. 55 relapsed/refractory HL cases treated with aHSCT in Ege Univer-
Methods: Patients who was underwent aHSCT at the Hospital sity Hospital between 2008-2014 were evaluated retrospectively.
of Ege University, Adult Hematology Department, Transplant Results: All the patients were mobilised after a salvage chemo-
Center between 2008 and 2014 were analyzed retrospectively. therapy regimen (ICE or ESHAP) combined with 10g/kg/day
Fify-six relapsed/refractory HL patients who was underwent dose of filgrastim. Poor mobilization was not observed. Mean
aHSCT were included to study. collection day after filgrastim administration was 6.1 days for
Results: The median age of the patients was 43 years (27-75 NHL group and 5.9 for HL group. Mean apheresis cycle was 2.3
years), and of 36 (64.2%) males and 20 (35.8%) females.Thirty- for NHL group, 2.4 for HL group. Mean total CD34+ HSCs num-
five (61.4%) of the patients were nodular sclerosis HL,14 were ber was 8.4x106 for NHL group and 7.9 x106 for HL group. There
(24.6%) mixed cellular HL,4 (7.0%) were lymphocyte predominant was no statistically difference between groups in terms of HSCs
HL,and 3 (5.3%) were lymphocyte-rich HL. All the patients were collection day, total apheresis cycle, and CD34+ HSCs number
mobilised after a salvage chemotherapy regimen (ICE or ESHAP) between groups. Mean neutrophil and platelet engraftment
combined with 10g/kg/day dose of filgrastim. Mean collection time was 11.7 and 15.7 days in NHL group, and 12.4 and 14.4
day after filgrastim administration was 5.6 days for female and in HL group, respectively. There was no statistically significant
6.1 for male. Mean apheresis cycle was 2.5 for female and 2.4 for difference between the groups.
male. Mean total CD34+ HSCs number was 8.7x106 for female Conclusion: Lymphoma type is not a predictor factor for HSC
and 7.5x106 for male. Poor mobilization was not observed in mobilization, harvest and engraftment. Larger study groups
any patient. There was no statistically difference between sex, and different parameters are needed to demonstrate predictor
mobilisation regimen and type of Hodgkin lymphoma in terms factors for mobilization and engraftment.
of HSCs collection day, total apheresis cycle and total CD34+
P62 bortezomib dexamethasone (26 patients), lenalidomide (78

patients) and bortezomib + immunomodulator (thalidomide
REAL WORLD DATA ON CLINICAL FEATURES, or lenalidomide) + dexamethasone (27 patients). During evalu-
PROGNOSIS AND OVERALL SURVIVAL POST ation, 337 patients were alive (68.9%) and 149 patients (30.5%)
AUTOLOGOUS STEM CELL TRASPLANTATION IN died (due to MM progression: 88%, ASCT-related: 2%, secondary
MULTIPLE MYELOMA IN THE ERA OF NOVEL AGENTS: malignancy: 2%); 3 patients did not have survival data. After a
A REPORT OF THE GREEK SOCIETY OF HEMATOLOGY median post-ASCT follow-up of 56 months (95% CI: 51.2-60.7),
IN 489 PATIENTS the median post-ASCT time to progression and post-ASCT sur-
Eirini KATODRITOU1, Anastasia POULI2, vival were 46 months (95% CI: 38-54) and 101 months (95%
Evangelos TERPOS3, Maria KOTSOPOULOU4, CI: 79-122), respectively. In the multivariate analysis, pre-ASCT
Sossana DELIMPASI5, Argiris S. SYMEONIDIS6, treatment with novel agents and post-ASCT consolidation and/
Dimitrios CHRISTOULAS7, Pavlina KONSTANTINIDOU1, or maintenance therapy predicted for longer survival, whereas
Meletios A. DIMOPOULOS3, Ioanna SAKELLARI8 the presence of del17p and/or t(4;14) predicted for shorter post-
1
Department of Hematology, Theagenion Cancer Hospital, ASCT survival (p<0.05).
Thessaloniki, Greece, 2Department of Hematology, St. Conclusion: In the era of novel agents, patients treated with
Savvas Oncology Hospital, Athens, Greece, 3Department ASCT enjoy prolonged survival outcomes. Pre-ASCT treatment
of Clinical Therapeutics, National and Kapodistrian with novel agents and any type of consolidation or maintenance
University of Athens, School of Medicine, Athens, Greece, therapy predict positively for post-ASCT survival, indicating the
4
Department of Hematology, Metaxa Cancer Hospital, importance of continuous treatment in MM. High risk features
Piraeus, Greece, 5Department of Hematology and Bone remain a strong negative predictor for post-ASCT survival.
Marrow Transplantation Unit, Evangelismos Hospital,
Athens, Greece, 6Hematology Division, Department of
Internal Medicine, University of Patras Medical School,
Patras, Greece, 7Department of Hematology, 251 General OTHER HEMATOLOGICAL
Air Force Hospital, Athens, Greece, 8Department of MALIGNANCIES AND TREATMENT
Hematology and Bone Marrow Transplantation Unit, G.
Papanikolaou General Hospital, Thessaloniki, Greece COMPLICATIONS
Objective: Autologous stem cell transplantation (ASCT) and P63
novel agent-based therapies have improved multiple myeloma
HEMATOLOGIC MALIGNANCIES IN AN AEGEAN
(MM) outcome. In the era of novel agents, prognostic factors for
ISLAND POPULATION: THE CASE OF CHIOS
post-ASCT survival are not clearly defined and data regarding the
role of post-ASCT consolidation/maintenance (C/M) therapy are Ioulia CHALIORI, Electra DIMITRAKOPOULOU,
inconclusive. Our aim was to describe real world data on clinical Ioannis STAMOULIS, Maria PAPADOPOULOU,
features, prognosis and post-ASCT survival of MM patients treated Christos POZIOPOULOS
with ASCT in Greece, in the era of novel agents. HematologyLab and Blood Bank Department, Chios General
Methods: We reviewed the medical files of 489 consecutive MM Hospital, Chios, Greece
patients (M/F: 278/211, median age: 56 years, range: 31-79 years;
ISS-1: 189, ISS-2: 141, ISS-3: 90, missing data: 69) treated with ASCT Objective: This study aims at recording the frequency of the
between 2000 and 2013 in seven Greek Hematology Centers. various sub-types of Hematologic Malignancies (HMs) in an island
Results: High risk cytogenetics, i.e. del17p and/or t(4;14), were population so as to draw a first round of comparisons regarding
found in 24/104 (23%) patients with available data; 220 (45%) their occurrence. The case of reference is the North Aegean island
patients received conventional treatment and 269 (55%) received of Chios, the fifth largest Greek island in terms of size and the
novel agent-based therapies. The median number of induction sixth in terms of population (51,390 habitants, year 2011). The
cycles was 4 (range: 1-9). The median number of pre-ASCT treat- study is designed so as to offer the basis for researches that may
ment lines was 1 (range: 1-3); 470 patients underwent single and relate the prevalence of different HMs to special genetic, social
19 tandem ASCT; 378 patients were mobilized with cyclophospha- and environmental conditions (e.g. poor quality of water). It is
mide + G-CSF, 79 patients with G-CSF alone and 32 patients with also expected that the study will inform health-related policies
multi-agent chemotherapy. The median number of CD34+ cells regarding, for example, the allocation of resources between
infused was 5.9x106/kg (range: 2.6-7.43x106/kg); 176 patients had central and remote (e.g. island) public health care facilities.
very good partial response (vgPR) pre-ASCT and 203 had vgPR Methods: Prevalence of HMs patients between 1-1-2011 and 30-
post-ASCT. Post-ASCT, 266 patients received consolidation and/ 6-2015. Sources: Chios state hospital archives, all private practice
or maintenance therapy (consolidation: 80, maintenance: 186); archives by hematologists (total of 2). Classification: WHO 2008.
consolidation and maintenance treatment included interferon Results: Total HMs: 308. Lymphoid Malignancies (LMs): 171
A or dexamethasone (36 patients), thalidomide (99 patients), (55%). Myeloid Malignancies (MMs): 138 (45%). LMs: 52 CLL/SLL,
37 PCN (27 MM, 10 MGUS), 15 HL, 13 FL (1 grade 3B), 12MZL, 10 P65

DLBCL-NOS, 10 T-LGL, 8LL/ALL, 4 LPL-MW, 3 MALT, 3 HCL, 1MF,
1 Angioimmunoblastic T-cell, 1HDCN, MMs: 53 MDS (23 RA, 2 WHAT IS YOUR TREATMENT? DISSEMINATED
RAS, 5 RN, 14 RCMD, 9 RAEB2), MPN=72 (46 ET, 17 PV, 6 CML, 3 HISTIOCYTIC SARCOMA
PM), 13 AML. Veysi ASOGLU1,Muhammet MADEN2, Ali GOKYER1,
Conclusion: The 4.5 year period prevalence seems to be too Mehmet Sevki UYANK2, Gulsum Emel PAMUK2
high in comparison to all available international standards and 1
Department of Internal Medicine, Edirne State Hospital,
therefore further study is needed. Edirne, Turkey, 2Department of Hematology, Trakya
University, Edirne, Turkey
P64 Introduction: Histiocytic sarcoma (HS) is a rare, but aggressive
and resistant hematopeietic malignancy. HS reflects the mor-
INVESTIGATION OF SEASONAL FREQUENCY
AND PATHOGENS IN FEBRILE NEUTROPENIA phological and immunophenotypic characteristics of mature
tissue histiocytes. Average presentation age is 44-55. Clinical
Seray KARAGOZ1,Ozan SALIM1, Orhan Kemal YUCEL1,
presentation often involves gastrointestinal tract, skin and soft
Utku ILTAR1, Ramazan ERDEM1, Ozge TURHAN2,
tissue, but has also wide range of extranodal areas such as bone,
Levent UNDAR1
lymph nodes, liver, spleen, lungs and CNS.
1
Department of Hematology, Akdeniz University, Antalya, Case: A 73-year-old female patient was admitted to our clinic
Turkey, 2Department of Infectious Diseases and Clinical with complaint of swelling in the left axilla. The physical examina-
Microbiology, Akdeniz University, Antalya, Turkey tion revealed left axillary lymphadenopathie. In the blood count
leukocyte 71300/uL, hemoglobin 10.1 g/dL, platelets 216000/uL,
Objective: Febrile neutropenia is the most frequent complication
in the biochemical analysis, LDH 279 U/L were detected. PET/CT
in patients with hematological malignancies. The most common
revealed increased FDG uptake in lymphadenopathies in the neck,
cause of mortality of patients with febrile neutropenia is infec-
tions. Fever during neutropenia may be the only sign of a severe left ear, nodular lesions on right hemithorax, the lower and upper
underlying infection. Infections can rapidly progress, leading to limb bone, and bone marrow of left tibia (SUVmax between 0.5
life - threatening complication. Therefore fever in neutropenic and 4.9). It was determined CD23 positive, LCA weak positive,
patients must be accepted as an infection and empiric wide CD68 strong positive, Ki67 70-80%, CD1a and CD21 negative
spectrum antibiotherapy must be iniated in order to avoid in the lymph node biopsy. According to present findings the
progression and possibly death. The aim of this study was to patient was diagnosed as Histiocytic Sarcoma (WHO-2008). It
examine demographical and clinical characteristics of patients, was initially started CHOP (cyclophosphamide, doxorubicin,
difference in frequencies of episodes between months and sea- vincristine, prednisone) regime.After second course of CHOP was
sons, distribution and frequency variance of isolated pathogens. observed progression in lesions. Additionally 4 courses of ICE
Methods: In this study 194 febrile neutropenic episodes of (ifosfamide, carboplatin, etoposide) regime were applied. First
105 patients with hematological malignancies who have been 15 days of ICE regime a significant regression was observed in
hospitalized between 1 June 2013 and 31 May 2014 in Akdeniz skin lesions, however reprogression was observed after 15 days.
University Faculty of Medicine, Hematology Department were A month after the forth course of ICE the patient died because
evaluated retrospectively. of febrile neutropenia and pneumonia.
Results: There was no difference in frequency of febrile neu- Conclusion: There is no standart treatment protocol for HS,
tropenic episodes between months (p = 0.564) and seasons because it is rarely seen. CHOP and ICE are the most preferred
(p = 0.345). There was no pathogen microorganism isolated in treatment regimens. It was demonstrated progression to CHOP
54.6% of febrile neutropenic episodes. In 45.4% of 194 febrile and ICE regime in the our case. HS is very rare subtype of NHL
neutropenic episodes pathogens were observed. 50.4% of all and should be detailed pathological examination, and further
agents was gram negative bacteria, 29.2% was gram positive, studies with case series are required to determine effective
13.3% was viral agents, 5.3% was fungi and 1.8% was parasites. treatment protocols.
The most frequent gram negative bacteria was E. Coli and the
most frequent gram positive bacteria was KNS.
Conclusion: This is the first study that examines FEN episodes
according to months and seasons as far as we know.
P66 had no history of immunosuppressive agent intake or HIV. They

both had sputum smear negativity and normal chest radiography.
MILIARY TUBERCULOSIS MIMICKING LYMPHOMA: They both had elevated transaminases and C-reactive protein.
A CASE REPORT
They both had anemia but the LDH levels were in normal limits.
Pelin AYTAN1,zkan HATEM2 The first case had massive splenomegaly and the second case
1
Mersin State Hospital, Department of Hematology, Mersin, had bilateral cervical, supraclavicular lymph nodes greater than
Turkey, 2Mersin State Hospital, Department of Radiology, 2 cm. In PET CT there were multiple lesions in the spleens and
Mersin, Turkey thoracal regions of both patients with increased FDG intensity.
While splenectomy was performed to the first case, cervical
Introduction: Miliary tuberculosis (MT) still remains a perplexing
lymphadenectomy was done to the second case. Both biopsy
disease that continues to elude the most experienced clinicians
and is a diagnostic and therapeutic challenge. We present two results were caseificated granulomatous inflammation. Anti-
cases of miliary tuberculosis that mimic lymphoma. Mortality tuberculosis treatment was administered for six months to both
from this disease has remained high despite effective therapy patients. They have been still following up at hematology clinic
being available. and there are regressions in the lesions.
Cases: The first case is a 27-year-old male who presented with Conclusion: MT is a disease that may mimic malignancies and is
fever with evening rise of temperature of several weeks of dura- not uncommon in developing countries. It should be considered
tion, anorexia, weight loss and weakness. He was a farmer. The in the differential diagnosis in patients with night sweats, anorexia,
second case is a 42-year-old female who presented with night weight loss and fever even in the patients with a positive PET
sweats, coughing but no heamoptysis. She was a tailor. They both scan. Biopsy is the method of diagnosis.

Acute Myeloid Leukemia

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tion. Combining verapamil with other chemotherapeutic drugs

P04 Objective: Myeloid sarcoma (MS) represents the proliferation

Objective: Identifying molecular aberrations in Acute Myeloid

with BMI. Our clinical prediction rule was adequately validated

which could be compatible with AVWS. There was an inverse P20

increased circulating PlGF and VEGFR-1. High VEGFR-1 correlated P41

was observed in one patient along with CALR mutation. DNMT3a

P46 of myelofibrosis and the need to start cytoreductive treatment.

Eight PMF patients (1.1% of all CMPN patients) were treated

P62 bortezomib dexamethasone (26 patients), lenalidomide (78

37 PCN (27 MM, 10 MGUS), 15 HL, 13 FL (1 grade 3B), 12MZL, 10 P65

P66 had no history of immunosuppressive agent intake or HIV. They

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