Biosimilar filgrastim (leucostim®) have similar efficacy in steady-state hematopoietic progenitor cell mobilization compared to original filgrastim (neupogen®) and lenograstim (granocyte®): A retrospective multicenter study.

Biosimilar filgrastim (Leucostim®) was shown to be similar in terms of efficacy and safety in hematopoietic progenitor cell mobilization (HPCM) compared to originator filgrastim (Neupogen®) and lenograstim (Granocyte®) in healthy donors and chemomobilization settings. Here we report our retrospective experience with Leucostim® (n: 43) compared to Neupogen® (n: 71) and Granocyte® (n: 32) in steady-state mobilization of patients presenting with Hodgkin lymphoma, non-Hodgkin lymphoma and multiple myeloma. The median age of patients on Leucostim® (56) arm was significantly higher compared to patients who received Neupogen® (50) and Granocyte® (49) (p: 0.039). Patients who underwent HPCM with Leucostim® received less chemotherapy lines (p: 0.026) and courses (p: 0.046) compared to others. Otherwise the study cohort was homogenous in terms of gender, primary diagnosis and various risk factors for mobilization failure. Mobilization failure was defined as failure to achieve a minimum threshold (10/µL) for peripheral blood CD34+ cell concentration to initiate leukapheresis or 0.5×106/kg, 0.8×106/kg and 2×106/kg CD34+ cells in first, second and fourth days of apheresis, respectively. The study groups were similar in terms of median number of CD34+ progenitor cell yield (×106/kg) (Neupogen®: 6.18, Granocyte®: 6.2 and Leucostim®: 6.2) (p: 0.959) and median number of leukapheresis sessions (p: 0.615). The treatment arms were also similar in terms of mobilization failure (Neupogen® 11.3% - Granocyte® 21.9% - Leucostim® 16.3%; p: 0.366). No patient experienced any severe adverse effect during HPCM. Leucostim® is equally effective and safe in HPCM compared to originator G-CSF (Neupogen®) and lenograstim (Granocyte®) in steady-state HPCM setting.

Does microbial contamination influence the success of the hematopoietic cell transplantation outcomes?

INTRODUCTION: Microbial contamination can be a marker for faulty process and is assumed to play an important role in the collection of hematopoietic progenitor cell (HPC) and infusion procedure. We aimed to determine the microbial contamination rates and evaluate the success of hematopoietic cell transplantation (HCT) in patients who received contaminated products. PATIENTS-METHODS: We analyzed microbial contamination records of HPC grafts between 2012 and 2015, retrospectively. Contamination rates of autologous donors were evaluated for at three steps: at the end of mobilization, following processing with dimethyl sulfoxide, and just before stem cell infusion. Grafts of allogeneic donors were assessed only before HCT. RESULT: A total of 445 mobilization procedures were carried out on 333 (167 autologous and 166 allogeneic) donors. The microbiological contamination of peripheral blood (323/333 donations) and bone marrow (10/333 donations) products were analyzed. Bacterial contamination was detected in 18 of 1552 (1.15 %) culture bottles of 333 donors. During the study period 248 patients underwent HCT and among these patients microbial contamination rate on sample basis was 1.3 % (16/1212). Microbial contamination detected in nine patients (7 autologous; 2 allogeneic). In 8 of 9 patients, a febrile neutropenic attack was observed. The median day for the neutropenic fever was 4 days (0-9). None of the patients died within the post-transplant 30 days who received contaminated products. CONCLUSION: The use of contaminated products with antibiotic prophylaxis may be safe in terms of the first day of fever, duration of fever, neutrophil, platelet engraftment and duration of hospitalization.

Does defibrotide prophylaxis decrease the risk of acute graft versus host disease following allogeneic hematopoietic cell transplantation?

There is some preliminary evidence, that veno-occlusive disease prophylaxis with defibrotide (DF) may also have a role in decreasing risk of acute graft-versus-host disease (aGvHD) by preventing tissue damage. In this study, we aimed to investigate the role of DF prophylaxis on the development of aGvHD at D+180. One hundred ninety-five consecutive adult patients receiving allogeneic HCT were retrospectively evaluated in 3 groups: no DF, DF/post-HCT (DF D+1 to D+14) and DF/pre-HCT (DF for 14 days concurrently with conditioning). The total (p: 0.057) and grades III/IV (p: 0.051) aGvHD rates at D+180 were 46.5%, 40%, 25.5% and 15.5%, 11.2%, 0% in patients on no DF, DF/post-HCT and DF/pre-HCT. DF may have a role in decreasing incidence and severity of aGvHD, especially if used concurrently with conditioning regimen.

First hematopoietic cell transplantation in Uzbekistan: Progress through education and cooperation.

HCT rates are one of the important parameters defining developmental stage of a given country. There is a steady increase in HCT activity on both sides of Atlantic. But in certain parts of the world, HCT activities have yet to begin. Here we report the history of the establishment of the first HCT center and its preliminary activity in Tashkent-Uzbekistan through close cooperation between Turkish Cooperation and Coordination Agency (TIKA) and Uzbekistan Ministry of Health. As of 2014, a total of 10 multiple myeloma patients successfully underwent autologous HCT in Uzbekistan. This encouraging project may be seen as a good example for other developing countries.

Finding the Optimal Conditioning Regimen for Relapsed/Refractory Lymphoma Patients Undergoing Autologous Hematopoietic Cell Transplantation: A Retrospective Comparison of BEAM and High-Dose ICE.

OBJECTIVE: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHCT) is a well-defined treatment modality for relapsed/refractory non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). Although there are several options in terms of conditioning regimens before AHCT, no one treatment is accepted as a standard of care. This study aimed to compare different conditioning regimens for the treatment of NHL and HL. MATERIALS AND METHODS: Medical records of 62 patients who had undergone AHCT following BEAM (BCNU, etoposide, cytarabine, and melphalan) and high-dose ICE (hICE; ifosfamide, carboplatin, and etoposide) conditioning regimens were analyzed retrospectively and compared in terms of efficacy and adverse effects. RESULTS: The study included a total of 29 and 33 patients diagnosed with relapsed/refractory NHL and HL, respectively. Patients received BEAM (n=37) or hICE (n=25) regimens for conditioning. One-year overall survival was 73±6% in all patients. One-year overall survival was 71±8% and 74±9% in the BEAM and hICE groups, respectively (p=0.86). The incidences of nausea/vomiting (grade ≥2) (84% vs. 44.7%; p=0.04) and mucositis (grade ≥2) (13% vs. 3%; p=0.002) were higher in the hICE group compared to the BEAM group. In addition, we witnessed significantly more hepatotoxicity of grade ≥2 (40% vs. 2.7%; p<0.005) and nephrotoxicity of grade ≥2 (48% vs. 2.7%; p<0.005) among patients who received hICE. Significantly more patients (n=4; 25%) in the hICE group experienced veno-occlusive disease (VOD) compared to the BEAM arm, where no patients developed VOD (p=0.01). CONCLUSION: There was no difference in terms of overall survival between the BEAM and hICE groups. We observed significantly more adverse effects among patients treated with hICE. The BEAM regimen seems to be superior to hICE in terms of toxicity profile with comparable efficacy in patients with relapsed/refractory NHL and HL.

Which regimen is better for stem cell mobilization of lymphoma patients?

Although chemotherapy combined with G-CSF is an effective method for hematopoietic stem cell mobilization, standard chemotherapy protocol leading to best stem cell yield is not defined. In our study, we aimed to assess the impact of chemotherapy choice on mobilization outcome in lymphoma patients. Patients were mobilized with cyclophosphamide (n:15), ASHAP (n:11) or VGEPP (n:12) protocols. Groups were similar according to collected CD34+ cell count, total nucleated cell count and median apheresis days. Five out of fifteen (33%) patients could not be mobilized in Cy group but there was only one failed mobilization attempt in both salvage groups (9% with ASHAP vs 8% with VGEPP). In conclusion, we showed that VGEPP and ASHAP are safe protocols in terms of stem cell mobilization and have similar mobilization capacity as cyclophosphamide alone.

Predicting the successful peripheral blood stem cell harvesting.

Several previously defined factors affecting the mobilization success include age, prior chemotherapy lines, exposure to myelotoxic agents, extended field radiotherapy and bone marrow infiltration with the primary disease. The purpose of this study was to retrospectively analyze the influence of the predictive factors for a successful peripheral stem cell mobilization. We enrolled a total of 145 patients into the study (non-Hodgkin lymphoma (n: 40), Hodgkin lymphoma (n: 36), myeloma (n: 64), solid tumors (n:5)) who received autologous stem cell transplantation between 2009 and 2012. In multivariate analysis only platelet count was found to be related with mobilization outcome (p<0.05). Knowing predictive factors for successful mobilization may be useful to define the best timing for mobilization and the most appropriate mobilizing agents for proper patient population.

Microbial contamination of hematopoietic progenitor cell products.

INTRODUCTION: Microbial screening for contamination is a part of hematopoietic progenitor cell (HPC) collection and infusion procedure. We aimed to find out our microbial contamination rates during collection, processing and infusion steps of HPC products. We also evaluated the clinical course of patients who received contaminated HPC products. PATIENTS-METHODS: We retrospectively analyzed microbial contamination records of HPC grafts between 2010 and 2012. HPC products of autologous donors were evaluated for contamination at three steps: at the end of mobilization, following processing with DMSO and just before stem cell infusion. Grafts of allogeneic donors were assessed only before HPC transplantation (HCT). Microbiological analysis of HPC samples were performed with an automated system (BacT/Alert®). RESULT: During the study period a total of 492 mobilization procedures were performed on 329 (214 autologous and 115 allogeneic) donors. Bacterial contamination has been detected in 103 of 1630 samples (6%). Ninety-seven out of 1162 blood samples (8%) from 265 patients who were treated with HCT were contaminated. Forty-six patients (41 autologous and 5 allogeneic) were transplanted with contaminated HPC products. During HCT 42 patients experienced febrile neutropenic attack and 34 of them had positive blood culture results. In none of these 34 patients the isolated pathogens were the same organisms with those found in the final contaminated stem cell product before stem cell infusion. None of the patients who received contaminated products died because of sepsis within the posttransplant 30days. There was no significant difference between patients who received contaminated and non-contaminated products in terms of the first day of fever, duration of fever, engraftment kinetics and duration of hospitalization. CONCLUSION: Our results suggest that microbial contamination of HPC products is an issue to be prevented, although it may not have a major impact on the general success of HCT.

Pandemic 2009 H1N1 influenza in patients with hematopoietic stem cell transplantation and hematologic malignancy: single center experience.

Although valuable information on many aspects of the pandemic 2009 H1N1 influenza came to light in a relatively short period of time, the disease course among immunocompromised patients is largely unknown. In this study, we present the results of active H1N1 surveillance in 32 patients who were treated at our hematology/stem cell transplantation clinic between December 2009 and January 2010. We also report the clinical and laboratory features of patients with laboratory-proven disease and try to define the impact of novel H1N1 disease on their outcome. Eight patients in the hematology clinic and 7 patients in the hematology/stem cell transplantation unit tested positive for pandemic H1N1 infection. Patients were treated with oral oseltamivir for 5-15 days. In 10 patients the infection was limited to the upper respiratory tract. But in 5 patients it was complicated with lower respiratory diseases. Three of them required intensive care support with mechanic ventilation and all died during follow-up. As the clinical and radiological findings of H1N1 infection are nonspecific in nature, we should have a high index of suspicion in immunocompromised patients. Therefore, beginning empiric oseltamivir therapy while waiting for laboratory results and increasing the dose/duration of therapy in laboratory-confirmed cases could be life saving.