Hematopoietic Stem Cell Transplantation

Biological consequences and physical complaints were compared for donors randomly assigned either to blood stem cell (BSC) or bone marrow (BM) donation. In the period 1994-1999, 61 consecutive donors were included. The BSC donors were given G-CSF 10 g/kg s.c., daily during 5 days before the first leukapheresis. Nineteen donors had one leukapheresis, 10 required two and one donor needed three leukaphereses in order to reach the target cell number of 2 ؋ 10 6 CD34 + cells/kg bw of the recipient. A median platelet nadir of 102 ؋ 10 9 /l was reached shortly after the last leukapheresis. Three weeks post harvest, 17 of 30 BSC donors had a mild leukopenia. Six had a leukopenia lasting more than a year before returning to normal values. Both groups were monitored prospectively through a standardised questionnaire completed by the donors. BSC donation was significantly less burdensome than BM donation and was preferred by the donors. The short-term risks of BSC mobilisation and harvest seem negligible. The potential long-term effects of G-CSF are unresolved and the donors must be followed closely.

Renal impairment is a common complication of multiple myeloma (MM). The estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula is the recommended method for the assessment of renal function in patients with MM with stabilized serum creatinine. In acute renal injury, the RIFLE (risk, injury, failure, loss and end-stage kidney disease) and Acute Renal Injury Network criteria seem to be appropriate to define the severity of renal impairment. Novel criteria based on eGFR measurements are recommended for the definition of the reversibility of renal impairment. Rapid intervention to reverse renal dysfunction is critical for the management of these patients, especially for those with light chain cast nephropathy. Bortezomib with high-dose dexamethasone is considered as the treatment of choice for such patients. There is limited experience with thalidomide in patients with myeloma with renal impairment. Thus, thalidomide can be carefully administered, mainly in the context of well-designed clinical trials, to evaluate if it can improve the rapidity and probability of response that is produced by the combination with bortezomib and high-dose dexamethasone. Lenalidomide is effective in this setting and can reverse renal insufficiency in a significant subset of patients, when it is given at reduced doses, according to renal function. The role of plasma exchange in patients with suspected light chain cast nephropathy and renal impairment is controversial. High-dose melphalan (140 mg/m 2) and autologous stem-cell transplantation should be limited to younger patients with chemosensitive disease.

This paper outlines the BMT activity in India and describes in some detail the transplant program at the Christian Medical College, Vellore. In September 2005, data from six transplant centers in India were collected and a total of 1540 transplants have been performed in a country of over one billion population. At the center in Vellore, from October 1986 to December 2006, a total of 626 transplants have been performed in 595 patients, with 28 patients having more than one transplant. Thalassemia accounted for a third of these transplants: the country has over 20 million carriers and 10 000 children are born each year with thalassemia major. The average cost of allogeneic BMT in India is around $15 000-20 000, and this is considerably lower than the cost in the West. India needs to develop more transplant centers with adequately trained personnel, as there is great need for them. Improvements in the economy mean that more patients can afford this treatment.

Engraftment syndrome (ES), characterized by fever, rash, pulmonary edema, weight gain, liver and renal dysfunction, and/or encephalopathy, occurs at the time of neutrophil recovery following hematopoietic cell transplantation (HCT). In this study, we evaluated the incidence, clinical features, risk factors, and outcomes of ES in children and adults undergoing first-time allogeneic HCT. Among 927 patients, 119 (13%) developed ES at a median of 10 days (interquartile range

HBsAg-negative/HBcAb-positive haematopoietic stem cell transplant (HSCT) recipients are at high risk of hepatitis B virus (HBV) reactivation. Allogeneic HSCT recipients from years 2000 to 2010 were evaluated in order to study the impact of being HBsAg-negative/ HBcAb-positive in this population. Overall, 137 of 764 patients (18%) were HBsAg-negative/HBcAb-positive before HSCT. Overall survival, non-relapse mortality (NRM), acute and chronic graft-vs.-host disease were similar in HBcAb-positive and HBcAb-negative patients. Reactivation occurred in 14 patients (10%) within a median of 19 months after HSCT (range 9-77). Cause-specific hazard for reactivation was decreased in the case of an HBV-immune/exposed donor (HR adjusted = 0.12; 95% CI, 0.02-0.96; p 0.045) and increased in patients who received rituximab treatment (HR adjusted = 2.91; 95%CI, 0.77-10.97; p 0.11). Competing risk analyses documented a protective role of an HBV-immune/exposed donor (p 0.041) and an increased probability associated with the length of treatment with cyclosporine (p <0.001) and treatment with rituximab (but not with low-dose rituximab prophylaxis, p <0.001 at each landmark point). No differences in overall survival and NRM were found between patients with and without HBV reactivation. The donor's immunity was independently and consistently associated with a decreased risk of HBV reactivation, while rituximab and cyclosporine treatments increased the probability.

Many studies reported an improved prognosis in the patients with Burkitt&#39;s lymphoma obviating the need of stem cell transplantation. However, prognosis of the advanced disease (i.e. Burkitt&#39;s cell leukemia) has not been reported with current treatment modalities except for a few prospective trials. The aim of this study is to compare the prognoses of the Burkitt&#39;s cell leukemia (BL) patients with similarly treated and not transplanted other types of acute lymphoblastic leukemia (ALL) patients and with ALL cases that underwent allogeneic stem cell transplantation (ASCT) in their first remissions. In this retrospective analysis, BL patients aged between 16 and 63 who admitted between 2000 and 2014 to Hacettepe or Gazi University Hospitals and treated with intensive therapies aiming cure were included in the study. All ALL patients who were treated with a similar protocol not including transplantation during the same period (NTxALL group) and all ALL patients who underwent ...

Purpose: To examine the concordance between pediatric patient's self-report and parent-report regarding a patient's quality of life (QoL) prior to and following hematopoietic stem cell transplantation (HSCT) and to identify potential medical and demographic covariates of concordance. Patients and Methods: Utilizing the PedsQL 4.0, the longitudinal QoL data were obtained from 68 pediatric HSCT patient-parent dyads prior to and up to two years post-transplantation. Results: Reliability based upon Intraclass Correlation Coefficients (ICC) indicates a parabolic pattern of concordance being significantly poorer in the acute phase of treatment 3 months post-HSCT, followed by a return to pre-transplant levels at subsequent assessments and a substantial rise at one-and two-year follow-up assessments (Baseline ICC 5 0.42; 3 months 5 0.11; 6 months 5 0.54). Paired t-tests further indicate that concordance was highest for observable domains of functioning (Physical and School) with greater inter-rater discrepancies on the subjective domains (Emotional and Social) of QoL at baseline and 6 months post-transplantation. Conclusion: Children typically rated their QoL as higher than parents at all time points and in virtually all domains; however, both perspectives are vital in providing a more accurate depiction of a patient's treatment experience. Dyads speaking the same language exhibited higher levels of QoL agreement than those that did not, while concordance among femalepatient-dyads was more disparate than male-patient-dyads. Such findings highlight the importance of implementing psychosocial assessments and possible interventions for patients and parents proactively during the HSCT to effectively address the impact of the treatment and recovery experiences.

amyotrophic lateral sclerosis motor neurons superoxide dismutase 1 a b s t r a c t Amyotrophic lateral sclerosis (ALS) is a rare and lethal neurodegenerative disease for which there is no effective medical treatment. Although riluzole, an N-methyl-D-aspartate receptor antagonist, has been shown to be reasonably safe for patients with ALS, the drug has been demonstrated to prolong median survival by only 2e5 months. There is mounting evidence that stem cell-based gene therapy is a promising treatment modality for patients with ALS. In this review, we focus on the types, sources, and doses of stem cells that have been shown to be effective for ALS patients, the differences in cytokines or chemokines secreted from these various stem cells, and the immune-modulation activity of stem cells as treatment for ALS.

AML patients (total 129; median age ¼ 50 years; range 16-72) in first CR received BU and melphalan (BU/Mel) as conditioning regimen before auto-SCT. In all, 82 patients (63.6%) received PBSCs and 47 patients (36.4%) received BM cells. The distribution of cytogenetic categories was conventionally defined as favorable (15.5%), intermediate (60.1%) and unfavorable (24.3%). With a median followup of 31 months, the 8-year projected OS and disease-free survival (DFS) was 62 and 56% for the whole population, respectively. The relapse rate was 46% and the non-relapse mortality was 4.65%. Although PBSC transplantation led to a faster hematological recovery than BM transplantation, in univariate analysis the stem cell source, cytogenetics and different BU formulations did not significantly affect OS and DFS, whereas age and the number of postremission chemotherapy cycles did have a significant effect on the clinical outcome. Multivariate analysis identified age o55 years as the only important independent predictor for OS and DFS. Our data suggest that BU/Mel, being associated with a low toxicity profile (mainly mucositis) and mortality, is an effective conditioning regimen even for high-risk AML patients in first CR undergoing auto-SCT.

Conventional cytogenetics and interphase fluorescence in-situ hybridization (FISH) identify a high-risk multiple myeloma (HRM) population characterized by poor outcomes. We analyzed these differences among HRM versus non-HRM after upfront autologous hematopoietic cell transplantation (autoHCT). Between 2008 and 2012, 715 patients with multiple myeloma with FISH and/or cytogenetic data with upfront autoHCT were identified in the Center for International Blood and Marrow Transplant Research database. HRM was defined as del17p, t(4;14), t(14;16), hypodiploidy (&lt; 45 chromosomes excluding -Y) or chromosome 1 p and 1q abnormalities; all others were non-HRM. Among 125 (17.5%) HRM patients, induction with bortezomib and immunomodulatory agents (imid) was higher compared to non-HRM (56% vs 43%, p &lt;0.001) with similar pre-transplant complete response (CR) (14% vs 16%, p 0.1). At day-100 post-transplant, ≥ very good partial response was 59% in HRM and 61% in non-HRM (p=0.6). More HRM pat...

Objectives: Bronchiolitis obliterans syndrome is a significant postallogeneic hematopoietic stem cell transplant problem. Recent data in lung transplant patients suggest an association with gastroesophageal reflux disease and bronchiolitis obliterans syndrome. We studied posthematopoietic stem cell transplant patients with bronchiolitis obliterans syndrome for gastroesophageal reflux disease and its response to a proton pump inhibitor. Materials and Methods: Seven postallogeneic hematopoietic stem cell transplant patients with bronchiolitis obliterans syndrome were studied. Gastroesophageal reflux disease was assessed by 24-hour pH monitoring with a Bravo catheter-free radio pH capsule. Patients with positive gastroesophageal reflux disease were started on omeprazole. Pretreatment and posttreatment pulmonary function tests were done at 3-month intervals. Results: Of 7 patients, 5 had positive results for gastroesophageal reflux disease (71%). Omeprazole had a disease-stabilizing effect on the patients' pulmonary function tests. Conclusions: Our study shows a significant association between bronchiolitis obliterans syndrome and gastroesophageal reflux disease in postallogeneic hematopoietic stem cell transplant patients. Use of omeprazole may have a diseasestabilizing effect in short-term follow-up.

Malignancies arising from biliary tract epithelia, or cholangiocarcinoma, are rare tumors that have a poor prognosis. The incidence of these tumors is gradually increasing in many countries. Recent advances have been made in identifying some of the risk factors, and the need for appropriate classification is emerging. The diagnosis of cholangiocarcinoma is often difficult and requires multiple complementary studies. The use of molecular approaches may improve the diagnostic utility of biliary cytology. Treatment of these tumors is complex, and there are many different treatment options. Although surgical resection can be curative, many patients with cholangiocarcinoma are diagnosed at an advanced stage when only palliative approaches can be used. Photodynamic therapy is emerging as a useful modality.

Multi-proxy approach was used to reconstruct the environmental conditions of remote lakes in the High Tatra Mountains (Slovakia) over the past few centuries (approximately 500-1000 years). Short sediment cores (*30 cm) taken from three morphologically similar glacial lakes distributed along altitudinal gradient (subalpine to alpine conditions) were analysed for organic matter content (LOI), diatoms and chironomids. Both descriptive and correlative approaches were used for analysing stratigraphical data. Predictive canonical correspondence analysis and co-correspondence analysis were applied to directly relate physical and biological proxies to each other. The relationship between LOI and biotic proxies was inconsistent across groups and lakes. Concordant patterns in diatom and chironomid composition were found in two non-acidified lakes. Common trends in those assemblages indicated major past environmental events such as the Little Ice Age, air pollution and lake acidification. In contrast, no relationship between the composition of diatom and chironomid assemblages was found in the formerly acidified lake, suggesting different responses of assemblages to acidification. While chironomids showed shifts that are attributable to recovery, diatoms assemblage remained relatively stable throughout the uppermost layers of the sediment record. On the other hand, climatic-driven changes in assemblages detected in the deeper layers were more pronounced in diatoms than in chironomids.

Cover: This is a photograph of a model posing as a patient with Hu-PNS. Hu-PNS usually runs a severe and subacute course, leaving the patient with severe disability within weeks to months from onset of symptoms. At the time of neurological presentation, approximately 70% of patients are not known with cancer. In more than 80% of the patients, an underlying tumor is ultimately detected, most often a small cell lung cancer.

We developed a clinical-scale cord blood (CB) cell ex vivo procedure to enable an extensive expansion of committed progenitors-colony-forming cells (CFCs) without impairing very primitive hematopoietic stem cells (HSCs). CD34 ++ cells, selected from previously cryopreserved and thawed CB units, were cultured in two steps (diluted 1:4 after 6 days) in the presence of stem cell factor (SCF), fms-related tyrosine kinase 3 ligand (Flt-3L), megakaryocyte growth and development factor (MGDF) (100 ng/ml each), granulocytecolony stimulating factor (G-CSF) (10 ng/ml) in HP01 serum-free medium. HSC activity was evaluated in a serial transplantation assay, by detection of human cells (CD45, CD33, CD19 and CFC of human origin) in bone marrow (BM) of primary and secondary recipient NOD/SCID mice 6-8 weeks after transplantation. A wide amplification of total cells (ϳ350-fold), CD34 + cells (ϳ100-fold), and CFC (ϳ130-fold) without impairing the HSC activity was obtained. The activity of a particular HSC subpopulation (SRC CFC ) was even enhanced.Thus, an extensive ex vivo expansion of CFCs is feasible without impairing the activity of HSCs. This result was enabled by associating antioxidant power of medium with an appropriate cytokine cocktail (i.e., mimicking physiologic effects of a weak oxygenation in hematopoietic environment).

Aplastic anemia, an unusual hematologic disease, is the paradigm of the human bone marrow failure syndromes. Almost universally fatal just a few decades ago, aplastic anemia can now be cured or ameliorated by stem-cell transplantation or immunosuppressive drug therapy. The pathophysiology is immune mediated in most cases, with activated type 1 cytotoxic T cells implicated. The molecular basis of the aberrant immune response and deficiencies in hematopoietic cells is now being defined genetically; examples are telomere repair gene mutations in the target cells and dysregulated T-cell activation pathways. Immunosuppression with antithymocyte globulins and cyclosporine is effective at restoring blood-cell production in the majority of patients, but relapse and especially evolution of clonal hematologic diseases remain problematic. Allogeneic stem-cell transplant from histocompatible sibling donors is curative in the great majority of young patients with severe aplastic anemia; the major challenges are extending the ben-efits of transplantation to patients who are older or who lack family donors. Recent results with alternative sources of stem cells and a variety of conditioning regimens to achieve their engraftment have been promising, with survival in small pediatric case series rivaling conventional transplantation results. (Blood.

Hematopoietic cell transplantation (HCT) is the only known curative therapy for many patients with lifethreatening hematologic and oncologic diseases. It is estimated that the National Marrow Donor Program Ò (NMDP) will facilitate 10,000 transplants by 2015, double the current number. To better understand the existing personnel and center infrastructure for HCT in the country and to address system capacity challenges to the future growth of HCT, the NMDP convened a diverse group of stakeholders and thought leaders representing HCT physicians, physician assistants, nurse practitioners, nurses, pharmacists, other healthcare providers, HCT program directors, hospital administrators, payors, and professional organizations. Working groups were formed to identify: capacity issues because of shortages in human resources, structural constraints, and patient access barriers including diversity and healthcare disparity challenges; recommendations to address challenges; and stakeholders to engage. This report details the deliberations and recommendations of a national symposium,

The Graft Processing subcommittee of the Worldwide Network for Blood and Marrow Transplantation wrote this guideline to assist physicians and laboratory technologists with the setting up of a cell processing laboratory (CPL) to support a hematopoietic stem cell transplant program, thereby facilitating the start-up of a transplant program in a new location and improving patient access to transplantation worldwide. This guideline describes the minimal essential features of designing such a laboratory and provides a list of equipment and supply needs and staffing recommendations. It describes the typical scope of services that a CPL is expected to perform, including product testing services, and discusses the basic principles behind the most frequent procedures. Quality management (QM) principles specific to a CPL are also discussed. References to additional guidance documents that are available worldwide to assist with QM and regulatory compliance are also provided.

In the last decade with widespread use of quantitative analyses in medical research, close co-operation between statisticians and physicians has become essential from the experimental design through all phases of complex statistical analysis. On the other hand, easy-to-use statistical packages allow clinicians to perform basic statistical analyses themselves. Since the software they most commonly use does not perform in depth competing risk analysis, we recommend an add-on package for the R statistical software. We provide all the instructions for downloading it from internet and illustrate how to use it for analysis of a sample dataset of patients who underwent haematopoietic stem cell transplantation for acute leukaemia.

Extracorporeal photopheresis (ECP) was given to 23 patients with steroid-refractory acute GVHD (aGVHD, grade II (n ¼ 10), III (n ¼ 7) or IV (n ¼ 6)). The median duration of ECP was 7 months (1-33) and the median number of ECP cycles in each patient was 10. Twelve patients (52%) had complete responses. Eleven patients (48%) survived and 12 died, 10 of GVHD with or without infections and two of leukaemia relapse. The average grade of GVHD was reduced from 2.8 (on the first day of ECP) to 1.4 (on day þ 90 from ECP) (P ¼ 0.08), and the average dose of i.v. methylprednisolone from 2.17 to 0.2 mg/kg/d (P ¼ 0.004). Complete responses were obtained in 70, 42 and 0% of patients, respectively, with grades II, III and IV aGVHD; complete responses in the skin, liver and gut were 66, 27 and 40%. Patients treated within 35 days from onset of aGVHD had higher responses (83 vs 47%; P ¼ 0.1). A trend for improved survival was seen in grade III-IV aGVHD treated with ECP as compared to matched controls (38 vs 16%; P 0.08). ECP is a treatment option for patients with steroid refractory aGVHD and should be considered early in the course of the disease.

Purpose: Cyclophosphamide and thioTEPA are frequently used simultaneously in high-dose chemotherapy regimens. During a pharmacokinetic study of 31 courses in 20 patients of cyclophosphamide and its activated metabolite 4-hydroxycyclophosphamide given in the combination cyclophosphamide–thioTEPA–carboplatin, a sharp decrease in 4-hydroxycyclophosphamide concentration was observed immediately after the start of the thioTEPA infusion. A drug-drug interaction was suspected. This putative interaction was investigated in this study. Methods: Possible sequence dependency, due to inhibition of the formation of 4-hydroxycyclophosphamide by thioTEPA, was investigated by altering the sequence of infusion in three patients (four courses) receiving high-dose chemotherapy with cyclophosphamide (1000 or 1500 mg/m2 per day), thioTEPA (80 or 120 mg/m2 per day) and carboplatin (265 or 400 mg/m2 per day) in short infusions for four consecutive days. The pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide were established. Possible inhibition of the metabolism of cyclophosphamide and thioTEPA was investigated in human microsomes. Results: A striking sequence dependency of the pharmacokinetics of 4-hydroxycyclophosphamide was observed. Administration of thioTEPA 1 h prior to cyclophosphamide resulted in decreased Cmax (−62%) and AUC (−26%) values of 4-hydroxycyclophosphamide compared to those of thioTEPA administered 1 h after cyclophosphamide. In human microsomes an inhibition of the conversion of cyclophosphamide to 4-hydroxycyclophosphamide by thioTEPA was observed at clinically relevant concentrations with an IC50 of 23 μM. No inhibition of the formation of TEPA by cyclophosphamide was observed. Conclusions: ThioTEPA strongly inhibits the bioactivation of cyclophosphamide and this may decrease both efficacy and toxicity. Our results seriously question the practice of the simultaneous continuous infusion of cyclophosphamide and thioTEPA and suggest that the sequencing and scheduling of these two agents in high-dose chemotherapy regimens may be of critical importance.

Objectives To describe longitudinally different sources of perceived social support by children and adolescents who undergo haematopoietic progenitor cell transplant (HPCT). Methods Thirty-six (20 males, 16 females) survivors of paediatric HPCT, aged 8-18 years (Mean = 11.73), were assessed pre-HPCT and 6 months, 1 year and 2 years post-HPCT. Survivors were compared with siblings (n = 22) during the last assessment. The Social Support Scale for Children (SSSC), a self-report measure, provided scores on perceived social support from parents, teachers, friends and classmates. Results Throughout the 2 years post-HPCT, perceived social support from all sources was generally higher for survivors than for population norms. Over time, both children and adolescents reported higher social support from parents than the normative values. Over time, children perceived higher support from teachers than did adolescents, whereas adolescents' perceived social support from classmates increased but children's decreased. Survivors and siblings did not differ significantly in their perceived social support 2 years post-BMT. Conclusions This exploratory study suggests that perceived parental support is equally important for children and adolescents but classmate and teacher social support varies with age. These developmental differences have important clinical implications for the care of these patients.

The CD34-positive cell: definition and morphology Cellular expression of the CD34 antigen identifies a morph o l ogi c a lly and immu n o l ogi c a lly heterogeneous cell population that is functiona lly ch a racteri zed by the in vi tro c a p a bi l i ty to gen era te cl onal aggrega tes derived from early and late progenitors and the in vivo capacity to reconstitute the myelo-lymphopoietic system in a supralethally irradiated host. 1-3 Im mu n o h i s toch emical studies have dem ons tra ted that the CD34 anti gen is stage but not l i n e a ge specific. In fact, indepen den t ly of the d i f feren ti a tive lineage, it is ex pre s s ed on ly by on togen eti c a lly early cell s. 4 For ye a rs a major ob s t acle to the morph o l ogical iden ti fic a ti on of p ut a tive hem a topoi etic stem cell has been the d i f f i c u l ty in sep a ra ting them from their direct progeny. The use of CD34 and other su i t a bl e cell surface markers (i.e. CD33, CD38, HLA-DR a n ti gens) in flu ore s cen ce-activa ted cells orti n g techniques or other cell separation methods has allowed considerable progress in this field. Positively selected, lineage committed CD34 + cells and more immatu re, lineage nega tive C D 3 4 + C D 3 3-H LAD R-cells are shown in F i g u re 1 and Figure 2, re s pectively. On May-Grünwald-Giemsa stained preparations, CD34 + cells are medium sized cells having large nuclei, eccen tri c a lly su rro u n ded by narrow rims of deep blue cytoplasm occ a s i on a lly con t a i n i n g cytoplasmic granules. Some normal CD34 + cell nu cl ei show one or more pale blue nu cl eo l i .

When clinical data are subjected to statistical analysis, a common question is how to choose an appropriate significance test. Comparing two independent groups with observations measured on a continuous scale, the question is typically whether to choose the two-samplet test or the Wilcoxon-Mann-Whitney test (WMW test). Similar results are often obtained, but which conclusion can be drawn if significance tests give highly different P -values? The t test is optimal for normally distributed observations with common variance and robust to deviations from normality if sample sizes are not very small. The WMW test makes no distributional assumptions, but depends heavily on equal shape and variance of the two distributions (homoscedasticity). We have compared the properties of the traditional two-sample t test, a modified t test allowing unequal variance, and the WMW test by stochastic simulation. All show acceptable behaviour when the two distributions have similar variance. When variances differ, the modified t test is superior to the other two.

Hematopoietic stem cell transplantation (HCT) is a potentially life-saving therapy for patients with malignant and nonmalignant disease states. This article reviews the current published literature on the dosing of pharmacologic agents used for HCT preparative regimens with specific focus on the obese patient population. The review found that dose adjustments for obesity have, to date, been based empirically or extrapolated from published data in the nontransplantation patient population. As a result, the Committee determined that clear standards or dosing guidelines are unable to be made for the obese population because Level I and II evidence are unavailable at this time. Instead, the Committee provides a current published literature review to serve as a platform for conditioning agent dose selection in the setting of obesity. A necessary goal should be to encourage future prospective trials in this patient population because further information is needed to enhance our knowledge of the pharmacokinetics and pharmacodynamics of conditioning agents in the setting of obesity.

Objectives and aim: Patients affected by hematological malignancies can often benefit from high dose chemotherapy followed by peripheral blood stem cells (PBSCs) transplantation. Different strategies have been used to mobilize an adequate number of PBSC, including granulocyte colony-stimulating factor (G-CSF) alone or chemotherapy plus G-CSF. In this study, we aimed to compare the efficacy profile of different G-CSF agents including filgrastim (Neupogen Ò ), biosimilar filgrastim (Leucostim Ò ) and Lenograstim (Granocyte Ò ) on CD34 + mobilization in patients who underwent autologous hematopoietic stem cell transplantation (autoHSCT). Materials and methods: We retrospectively analysed data of patients who underwent auto-HSCT diagnosed with multiple myeloma (MM), Hodgkin Lymphoma (HL), non-Hodgkin Lymphoma (NHL) and others. Data for stem cell mobilization has been obtained from patients' files. Patients who received Filgrastim (Neupogen Ò ), biosimilar Filgrastim (Leucostim Ò , Group) and Lenograstim (Granocyte Ò ) were evaluated mainly for total CD34 + cell count at the end of mobilization procedure. Results: A total of 96 patients who underwent autoHSCT were retrospectively analyzed. 27 (28.2%) of the patients were female, and 69 (71.8%) were male. The diagnosis of the patients were; multiple myeloma (39 patients, 40.6%), Hodgkin Lyphoma (23 patients, 23.9%), non-Hodgkin lymphoma (16 patients, 16.6%), and others (18 patients, 18.9%). The median number of leukapheresis cycle necessary to harvest a minimal count of 3 Â 10 6 CD34 + /kg was 2 in Neupogen Ò (min-max: 1-4) and Granocyte Ò (min-max: 1-3) groups and 1 (min-max: 1-2) in Leucostim Ò group. The median doses of G-CSF agents (lg/kg/day) in PBSC collection procedure were; 10.00 (min-max: 7.00-12.00) in the Neupogen Ò group, 8.00 (min-max: 7.25-9.00) in the Leucostim Ò group and 8.50 (6.00-9.50) in the Granocyte Ò group. There was no statistical significance among groups (p = 0.067). The number of total collected PB CD34 + cells (Â10 6 /kg) was 7.64 (min-max: 4.09-13.86) in the Neupogen Ò group, 13.43 (min-max: 8.15-23.38) in the Leucostim Ò group and 5.45

Multi-proxy approach was used to reconstruct the environmental conditions of remote lakes in the High Tatra Mountains (Slovakia) over the past few centuries (approximately 500-1000 years). Short sediment cores (*30 cm) taken from three morphologically similar glacial lakes distributed along altitudinal gradient (subalpine to alpine conditions) were analysed for organic matter content (LOI), diatoms and chironomids. Both descriptive and correlative approaches were used for analysing stratigraphical data. Predictive canonical correspondence analysis and co-correspondence analysis were applied to directly relate physical and biological proxies to each other. The relationship between LOI and biotic proxies was inconsistent across groups and lakes. Concordant patterns in diatom and chironomid composition were found in two non-acidified lakes. Common trends in those assemblages indicated major past environmental events such as the Little Ice Age, air pollution and lake acidification. In contrast, no relationship between the composition of diatom and chironomid assemblages was found in the formerly acidified lake, suggesting different responses of assemblages to acidification. While chironomids showed shifts that are attributable to recovery, diatoms assemblage remained relatively stable throughout the uppermost layers of the sediment record. On the other hand, climatic-driven changes in assemblages detected in the deeper layers were more pronounced in diatoms than in chironomids.

Hematopoietic stem cell transplantation (HSCT) is the definite treatment for patients with thalassemia major. A busulfan (Bu) and cyclophosphamide (Cy)ebased regimen has been the standard myeloablative chemotherapy, but it is associated with higher treatment-related toxicity, particularly in patients classified as high risk by the Pesaro criteria. Treosulfan-based conditioning regimens have been found to be equally effective and less toxic. Consequently, we analyzed the safety and efficacy of treosulfan/thiotepa/fludarabine (treo/ thio/flu)-based conditioning regimens for allogeneic HSCT in patients with thalassemia major between February 2010 and September 2012. We compared those results retrospectively with results in patients who underwent previous HSCT with a Bu/Cy/antithymocyte globulin (ATG)ebased conditioning regimen. A treo/ thio/flu-based conditioning regimen was used in 28 consecutive patients with thalassemia major. The median patient age was 9.7 years (range, 2-18 years), and the mean CD34 þ stem cell dose was 6.18 Â 10 6 /kg. Neutrophil and platelet engraftment occurred at a median of 15 days (range, 12-23 days) and 21 days (range, 14-34 days), respectively. Three patients developed veno-occlusive disease, 4 patients developed acute graftversus-host disease (GVHD), and 2 patients had chronic GVHD. Treatment-related mortality (TRM) was 21.4%. Two patients experienced secondary graft rejection. We compared these results with results in patients who underwent previous HSCT using a Bu/Cy/ATG-based conditioning regimen. Twelve patients were treated with this protocol, at a median age of 7.2 years (range, 2-11 years). One patient had moderate veno-occlusive disease, 2 patients developed acute GVHD, 2 patients had chronic GVHD, and 2 patients experienced graft rejection. There was no TRM in this group. We found no significant differences between the 2 groups (treo/ thio/flu vs Bu/Cy/ATG) in terms of the incidence of acute GVHD, chronic GVHD, TRM, and graft failure, although a trend toward higher TRM was seen with the treo/thio/flu regimen. Ó

The purpose of this exploratory study is to better understand the current dynamics of the Malaysian market for smartphone and the usage behaviors of consumers. This paper presents the result of a survey on the trend of smartphone from the perspective of end consumers. The data was collected from 1814 respondents across major cities in Malaysia. This study has looked into the familiarity of users towards smartphones, choices of smartphone brand and service providers, and most importantly the determinants that influence their purchasing decision. Additionally, the consumers' preferences on smartphone specifications such as design, computing power, operating platform, and price were investigated. Furthermore, consumers' usage behaviors such as using smartphone for email, web browsing, gaming, and document reading were examined. The statistics presented provides fundamental information regarding the trends in the smartphone market and usage behaviors in Malaysia. Such information are useful for academics for the development of future works in the field, whereas for smartphone manufacturers, application developers and other stakeholders, they are able to plan their direction in the Malaysian smartphone market.