Papers by Cerasela Jardan
Documenta Haematologica - Revista Romana de Hematologie, Dec 17, 2023
Lineage switch in acute leukemias is considered a rare event, especially in what concerns adult d... more Lineage switch in acute leukemias is considered a rare event, especially in what concerns adult disease compared to pediatric patients. Differential diagnosis between biphenotypic/bilineal leukemias, de novo leukemias, therapy-related and phenotype switch variants, stands as an intricate challenge. Complementary laboratory studies and complex laboratory assays (conventional karyotyping, FISH-fluorescence in situ hybridization, molecular biology, immunophenotyping, etc.) represent one of the crucial resources regarding the process of establishing an accurate diagnosis, thus having a firm ground for the most beneficial treatment choice. Aim: To emphasize the diagnostic and therapeutic particularities regarding the case of a female patient with acute lymphoblastic leukemia (ALL) who later developed a phenotype switch towards an intermediary form of acute myeloid leukemia (AML), sharing features of both AML with maturation and atypical acute promyelocytic leukemia (AML M2/M3/APL). Material and methods: We hereby present the case of a 66 year old female, diagnosed with BALL , who underwent both classical chemotherapy (adequate protocol related to age, genetic profile, commorbidites) and bispecific monoclonal antibody therapy at first early relapse (Blinatumomab), followed by phenotype switch at second early relapse towards atypical APL. Combined ATRA and anthracycline therapy followed, yet laboratory work-up shows refractory disease. Complications during treatment were comprised of severe DIC (disseminated intravascular coagulation) and infections-sepsis followed by exitus. Results and conclusions: This is the case of a phenotype switch in a patient with ALL, who underwent both classical chemotherapy and Blinatumomab, towards myeloid lineage-refractory APL atypical variant. Availability of flow cytometry and cytogenetics during morphology evaluation represents a key aspect in the management of such hematologic malignancies.
Clinical Lymphoma Myeloma and Leukemia
The purpose of this work is to present the results of allogeneic stem cell transplantation as the... more The purpose of this work is to present the results of allogeneic stem cell transplantation as therapy for patients diagnosed with acquired aplastic anemia in the Department of Bone Marrow Transplantation of Fundeni Clinical Institute and to elaborate an algorithm of treatment in aplastic anemia starting with the observations obtained from our clinical practice and following the European treatment guidelines in this group of patients. Aplastic Anemia (AA) is a rare hematological disease characterized by pancytopenia and a hypocellular bone marrow. The paradigm of bone marrow failure syndromes, aplastic anemia is a diagnosis of exclusion despite the precision of its diagnosis criteria. Although AA is not a malignant disease, but an autoimmune disorder, the grave consequences of pancytopenia and clonal transformation into acute leukemia make it a potentially fatal condition. The management of AA patients is challenging and necessitates a very well established treatment plan from the di...
Fluorescent in situ hybridization (FISH) technique is increasingly used for the identification of... more Fluorescent in situ hybridization (FISH) technique is increasingly used for the identification of BCR/ABL gene rearrangements in chronic myeloid leukemia (CML).Patients and Methods: Both typical and atypical pattern of BCR/ABL gene rearrangements was determined in 83 patients with CML referred to Fundeni Clinical Institute using dual fusion fluorescence in situ hybridization (DF-FISH) probes and conventional cytogenetics.Results: in the majority of cases-82 out of 83-CML patients exhibited a translocation between chromosome 9 and 22, resulting in a Philadelphia chromosome and one patient, negative for the Ph chromosome, presented cryptic BCR/ABL rearrangement. All samples were analyzed both by FISH and conventional cytogenetics. In 71 out of 83 cases the typical interphase FISH signal patterns of BCR/ABL gene rearrangements was identified-one red signal, one green signal and two fusion signals (1R1G2F). The rest of 11 patients presented an atypical interphase FISH pattern. Atypical patterns included: loss of terminal region of derivative chromosome 9 (five patients), loss of derivative chromosome 9 (del(9q)der) (three patients), isodicentric 22 derivative chromosome fused at terminal region of q arm (one patient), isoderivative chromosomes 22 (ider(22)t(9;22) (q34;q11)) (one patient) and supernumerary Philadelphia (one patient).Conclusion: FISH technique exhibited an advantage of being simple and still allowing the identification of cryptic BCR-ABL insertion or variant Ph. Another advantage of this technique is that it allows examination of interphase nuclei in cases were no metaphases could be obtained and atypical patterns may have clinical prognostic implication.
Medicina
Background and Objectives: Despite the vast heterogeneity in the genetic defects causing hemophil... more Background and Objectives: Despite the vast heterogeneity in the genetic defects causing hemophilia A (HA), large intron inversions represent a major cause of disease, accounting for almost half of the cases of severe HA worldwide. We investigated the intron 22 and intron 1 inversion status in a cohort of Romanian unrelated patients with severe HA. Moreover, we evaluated the role of these inversions as relative risk factors in inhibitor occurrence. Materials and Methods: Inverse shifting—a polymerase chain reaction method was used to detect the presence of intron 22 and intron 1 inversions in 156 Romanian patients with HA. Results: Intron inversion 22 was found in 41.7% of the patients, while intron 1 inversion was detected in 3.2% of the patients. Overall, large intron inversions represented the molecular defect in 44.9% of the studied patients. Our findings are in accord with previously published reports from Eastern Europe countries and with other international studies. The risk ...
PubMed, Apr 29, 2015
Multiple myeloma and JAK2 positive chronic myeloproliferative neoplasms are hematologic malignanc... more Multiple myeloma and JAK2 positive chronic myeloproliferative neoplasms are hematologic malignancies with a completely different cellular origin. Two cases of simultaneous occurrence of multiple myeloma, one with primary myelofibrosis and another one with essential thrombocythemia are reported in this article. In such cases, an accurate diagnosis requires a molecular testing, including gene sequencing and differential diagnosis of pancytosis associated with splenic amyloidosis. In general, in such cases, of two coexisting malignant hematologic diseases, the treatment of the most aggressive one is recommended. For our two cases, it was decided to start a Velcade based therapy. The main concern was the medullar toxicity, especially when a multiple myeloma was associated with a primary myelofibrosis.
PubMed, Dec 15, 2015
Background: Chronic Myeloid Leukemia's (CML) treatment was optimized since the development of tyr... more Background: Chronic Myeloid Leukemia's (CML) treatment was optimized since the development of tyrosine kinase inhibitors (TKI) and an increased overall survival during TKI was noticed. During the TKI era, protocols for assessing response and resistance to treatment were developed. Additional chromosomal abnormalities (ACAs) are strongly associated with disease progression but their prognostic impact and influence on treatment response are yet to be defined. The aim of this study was to analyze the impact of ACAs on time to achieve complete cytogenetic response (CCyR), treatment and overall survival. Materials and methods: Since 2005 until 2013, the data from the Hematology and Bone Marrow Transplantation Department of Fundeni Clinical Institute was collected. In this observational retrospective single centre study, 28 CML patients with ACAs at diagnosis and during TKI treatment were included. Results: From ACAs at diagnosis group, the most frequent major route ACAs were trisomy 8, trisomy 19 and second Philadelphia (Ph) chromosome and the most frequent minor route ACAs were monosomies and structural abnormalities (inversions and translocations). From the ACAs during the TKI group, the most frequent major route cytogenetic abnormalities in Ph positive and negative cells were trisomy 8, trisomy 19 and second Ph chromosome and the most frequent minor route cytogenetic abnormalities in Ph positive and negative cells were marker chromosomes and structural abnormalities (inversions, translocations and dicentric chromosomes). Conclusions: In both groups, the time to CCyR was longer and long-term results were inferior in comparison with standard patients but the differences were not significant and in accordance to published data. The 12 months follow-up after the study's end showed that 26 patients were alive and in long-term CCyR and 2 deaths were reported. Abbreviations: CML = Chronic Myeloid Leukemia, BCR-ABL1 = Break Cluster Region - Abelson gene, TKI = tyrosine kinase inhibitor treatment, ACAs = additional cytogenetic abnormalities, CCyR = complete cytogenetic response, PCyR = partial cytogenetic response, mCyR = minor cytogenetic response, MMR = major molecular response, HSCT = hematopoietic stem cell transplant, HLA = human leukocyte antigens, CP = chronic phase, AP = accelerated phase, BP = blast phase, OS = overall survival, CBA = chromosome banding analysis, +8 = trisomy 8, i(17q) = isochromosome (17q), +Ph = second Philadelphia chromosome, -7 = monosomy 7, -17 = monosomy 17, +17 = trisomy 17, -21 = monosomy 21, +21 = trisomy 21, -Y = loss of Y chromosome, ELN = European LeukemiaNet, IMA600 = Imatinib 600 mg daily, IMA400 = Imatinib 400 mg daily, NILO600 = Nilotinib 600 mg daily, DASA100 = Dasatinib 100mg daily, DASA140 = Dasatinib 140 mg daily.
Leukemia Research, May 1, 2013
Documenta Haematologica - Revista Romana de Hematologie
Introduction: miRNAs are involved in the pathogenesis of neoplastic syndromes by silencing target... more Introduction: miRNAs are involved in the pathogenesis of neoplastic syndromes by silencing target genes. As previously shown, hsa-mir-4328 is downregulated in Acute Promyelocytic Leukemia (APL). Objectives: The study aims to identify the somatic mutations of the MIR-4328 gene that caused its downregulation in APL and their localization in key regions of the mature miRNA structure. Material and methods: The study included 24 subiects: the study group (10 patients at the onset of APL, as well as at remission and relapse) and the control group (10 apparently healthy patients). High-Resolution Melting (HRM) was used for genotyping. Results: As MIR-4328 gene has not been studied before, a structure design of the coding region was performed to better understand the impact of somatic mutations on the mature miRNA. Following HRM, 2 mutant genotypes were identified, different from the wild-type (WT) genes. Conclusions and discussion: Due to the major deviation of the mutant genotypic curves ...
The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion t... more The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion transcript of the promyelocytic leukemia gene with the retinoic acid receptor α gene (PML::RARA), which is a molecular target for all-transretinoic acid (ATRA) and arsenic trioxide (ATO). Therapies with ATRA plus ATO have excellent outcomes in terms of complete remission rate, overall survival, and achievement of a deep and durable molecular response with a very low incidence of relapse. However, although the combination of ATRA and ATO has lower hematologic toxicity than standard chemotherapy, its use is associated with a spectrum of unique toxicities, such as hepatic toxicity, QTc (QT interval corrected) prolongation, neurotoxicity, and differentiation syndrome. Hematologists treating patients with acute promyelocytic leukemia should be aware of possible early-complications of the ATRA plus ATO regimen and aim to balance treatment-related adverse events and efficacy. Careful follow-up o...
Journal of Clinical Medicine, Feb 11, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Clinical Lymphoma Myeloma and Leukemia
Romanian Journal of Medical Practice, 2015
The authors studied the outcome of a cohort of pediatric acute lymphoblastic leukemia (ALL) patie... more The authors studied the outcome of a cohort of pediatric acute lymphoblastic leukemia (ALL) patients (33 children and adolescence) diagnosed and treated conforming to modern Chemotherapy Protocols (ALL ICBFM 2002, Interfant 06) in a single Center – Pediatric Clinic, Fundeni Clinical Institute, Bucharest, Romania. They analyzed the factors which determine the prognosis and the outcome of these patients in the course of multi-agent systemic chemotherapy to stand at the base of these Protocols: initial age, initial leukocyte count, blasts immunophenotype, cytogenetic and molecular abnormalities, initial response to cortisone, risk groups, time to obtain the complet remission, etc. Among the factors they discussed, a great value was proven to have the minimal residual disease (MRD) determination in certain check points of Protocols and revaluation of patients risk conforming to MRD values. Using the modern Protocols and continuously watching the evolution on therapy enable the authors t...
Documenta Haematologica, May 1, 2015
The purpose of this work is to present the results of allogeneic stem cell transplantation as the... more The purpose of this work is to present the results of allogeneic stem cell transplantation as therapy for patients diagnosed with acquired aplastic anemia in the Department of Bone Marrow Transplantation of Fundeni Clinical Institute and to elaborate an algorithm of treatment in aplastic anemia starting with the observations obtained from our clinical practice and following the European treatment guidelines in this group of patients. due to older age, the immunosuppression with ATG and cyclosporine is an efficient treatment. The supportive care has an important role and the patients with aplastic anemia should be managed by a multidisciplinary team. For patients older than 40 years, the choice between immunosuppressive therapy (IST) and upfront transplant with HLA identical sibling donor remains a key question. However, the standard approaches for this category of patients is front line immunosuppression with ATG and cyclosporine and if they become refractory to at least one course of IST the allogeneic stem cell transplant using fludarabine-based conditioning is the second-line treatment option. In our institution there were eleven AA patients treated with allogeneic stem cell transplantation from 2009 till 2015. They were all young patients with age between 19 and 42 years old and all had severe acquired aplastic anemia with transfusion dependence. Six cases were transplanted from a matched sibling donor and five patients had undergone an unrelated matched donor transplant. The allogeneic HSCT procedure was done both as front line therapy in the case of three patients and as second treatment choice in the rest of eight patients. Four patients died, three of them due to transplant related toxicity and one patient experienced severe autoimmune reaction with transfusion inefficacy complicated with intracerebral haemorrhage at four months from transplant. In our opinion the most challenging aspect in treating AA patients is choosing the best treatment option taking into account the patient age and performance status, the severity of the disease and the availability of a donor for allogeneic HSCT. Although the treatment strategy must be individualized in every patient case, it is necessary to make a standardization of treatment procedures in AA and to follow the evidence based recommendations available in the management of this rare disease.
Frontiers in Medicine, Mar 22, 2022
Documenta Haematologica, 2015
Background: Aplastic anemia (AA) is a rare and serious disease characterized by pancytopenia and ... more Background: Aplastic anemia (AA) is a rare and serious disease characterized by pancytopenia and hypoplastic bone marrow in the absence of infiltrates/fibrosis. It occurs more frequently in childhood and young adulthood (10-30 years) and with older age (>60 years), with equal distribution among men and women. As hypoplastic myelodysplastic syndromes (hMDS) are also associated with cytopenia and hypocellular marrow,they may be difficult to differentiate from AA. The presence of dysplastic features (others than erythroid) and/or blast cells >5% is essential to distinguish hMDS from AA. Cytogenetic tests may reveal clonal evolution in hMDS. As the two disorders differ greatly in means of management and prognosis, the correct diagnostic is very important. Case presentation: We report the case of a 39 years old female diagnosed in 2005 (at age 29) with aplastic anemia. She received treatment with corticosteroids, Cyclosporine, blood transfusions and growth factors with partial resp...
Journal of Medicine and Life, 2012
Acute myeloid leukemia (AML) is a heterogeneous disease in clinical presentation, outcome and the... more Acute myeloid leukemia (AML) is a heterogeneous disease in clinical presentation, outcome and therapeutic response. Cytogenetic and molecular characteristics are important prognostic indicators allowing the identification of distinct subtypes of AML, prognostic stratification and risk-adapted treatment. We present our experience during 5 years, in which we treated 245 patients with AML, of which we could genetically characterize 48 cases (26 females, 22 males) with a median age of 52 years. Cytogenetic analysis was performed by GTG banding on cultures of marrow cells treated with colcemid. Molecular analysis used RT-PCR performed on ABI 9700 platform in order to identify the following fusion genes: E2A-PBX1, TEL-AML1, AML1-ETO, PML-RARα, MLL-AF4, CBFC-MYH11, BCR-ABL, SIL-TAL, and MLL-AF9as well as mutations in Flt3, NPM1, WT1 genes. Fourteen patients were older than 60 years. In 12 we performed cytogenetic analysis showing 5 cases with complex karyotype, 2 normal karyotypes, 1 case ...
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Papers by Cerasela Jardan