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Background: Turkish Stem Cell Coordination Center (TURKOK) carries out the procurement process of unrelated allogeneic hematopoietic stem cells in Turkey. This study aims to compare the efficacy of both once‐daily and divided‐dose G‐CSF administration and the original and biosimilar G‐CSF use and the frequency and severity of adverse events in TURKOK donors. Method: The study was conducted retrospectively with 142 healthy TURKOK donors. For PBSC mobilization, two different subcutaneous G‐CSF programs were used as 10 μ/kg/day single‐dose and 5 μ/kg/12 h. Neupogen (Amgen, Puerto Rico) and Tevagrastim (Teva, Kfar Saba, Israel) were used as G‐CSF. All donors started apheresis on the fifth day, and all side effects were recorded during the procedure. Results: Stem cell yield was similar between single‐dose and divided‐doses based on donor weight, favoring the split‐dose based on recipient weight (P =.506 and P =.023, respectively). Both G‐CSF posologies were comparable if the target CD34+ cell yield was ≥4 × 106/kg. CD34+ cell yield was equivalent when evaluated against recipient weight, significantly favoring Tevagrastim vs Neupogen by donor weight (P =.740 and P =.021, respectively). Side effects, duration of pain, and need for analgesia favor Tevagratim over Neupogen. Conclusion: Split‐dose may be recommended for cases where the need for large numbers of CD34+ cells to be harvested is anticipated due to significant cell yield relative to recipient weight. However, sufficient hematopoietic stem cells can be collected with both posology. Tevagrastim is non‐inferiority effective to Neupogen. Side effects during administration are both low‐grade and temporary. [ABSTRACT FROM AUTHOR]

In April 2014, the Japan Society for Hematopoietic Cell Transplantation started a prospective observational study entitled "A short-term follow-up investigation of related hematopoietic stem cell donors receiving biosimilar G-CSF to mobilize peripheral blood stem cells." A total of 106 donors were registered from 25 transplant facilities through the end of March 2017. The study cohort consisted of 47 men and 58 women, and their median age was 38.5 years (range 15–65 years). The mean total count of collected CD34-positive cells/recipient body weight for all 106 donors was 4.40 ± 2.38 × 10 6/kg. The yield of CD34-positive cells was weakly correlated with donor age was observed. However, gender, WBC count on day 4, G-CSF dose reduction, type of apheresis device, collection speed, and treated blood volume had no significant impact on the collection efficacy of CD34-positive cells. The safety profile of biosimilar G-CSF was also acceptable: 126 adverse events in 73 donors were reported, but none was serious. The most common adverse events were low back pain, headache, and bone pain. This prospective study confirmed that biosimilar G-CSF had comparable efficacy and safety to reference G-CSF for CD34-positive cell mobilization in healthy related donors. [ABSTRACT FROM AUTHOR]

The World Marrow Donor Organization recommends original granulocyte-colony stimulating factor (G-CSF) for the mobilization of stem cells in healthy unrelated hematopoietic stem cell donors. We report the comparison of a biosimilar G-CSF (Zarzio) with two original G-CSFs (filgrastim and lenograstim) in mobilization in unrelated donors. We included data of 313 consecutive donors who were mobilized during the period from October 2014 to March 2016 at the Medical University of Warsaw. The primary endpoints of this study were the efficiency of CD34+ cell mobilization to the circulation and results of the first apheresis. The mean daily dose of G-CSF was 9.1 μg/kg for lenograstim, 9.8 μg/kg for biosimilar filgrastim, and 9.3 μg/kg for filgrastim (p < 0.001). The mean CD34+ cell number per microliter in the blood before the first apheresis was 111 for lenograstim, 119 for biosimilar filgrastim, and 124 for filgrastim (p = 0.354); the mean difference was even less significant when comparing CD34+ number per dose of G-CSF per kilogram (p = 0.787). Target doses of CD34+ cells were reached with one apheresis in 87% donors mobilized with lenograstim and in 93% donors mobilized with original and biosimilar filgrastim (p = 0.005). The mobilized apheresis outcomes (mean number of CD34+ cells/kg of donor collected during the first apheresis) was similar with lenograstim, biosimilar filgrastim, and filgrastim: 6.2 × 106, 7.6 × 106, and 7.3 × 106, respectively, p = 0.06. There was no mobilization failure in any of the donors. Biosimilar G-CSF is as effective in the mobilization of hematopoietic stem cells in unrelated donors as original G-CSFs. Small and clinically irrelevant differences seen in the study can be attributed to differences in G-CSF dose and collection-related factors. Active safety surveillance concurrent to clinical use and reporting to donor outcome registry (e.g., EBMT donor outcome registry or WMDA SEAR/SPEAR) might help to evaluate the possible short- and long-term complications of biosimilar G-CSF. [ABSTRACT FROM AUTHOR]

Background and Objectives Biosimilars of the granulocyte colony stimulating factor (G- CSF) filgrastim were approved by the European Medicines Agency ( EMA) for registered indications of the originator G- CSF, including prevention and treatment of neutropenia, as well as mobilization of peripheral blood stem cells in 2008. Nevertheless, there is still an ongoing debate regarding the quality, efficacy and safety of biosimilar G- CSF. Materials and Methods This article is a meta-analysis of clinical studies on the use of biosimilar G- CSF for mobilization and transplantation of haematopoietic stem cells as available in public databases. All data sets were weighted for the number of patients and parameters and then subjected to statistical meta-analysis employing the Mann-Whitney U-test followed by the Hodges-Lehmann estimator to assess differences between biosimilar and originator G- SCF. Results A total of 1892 individuals, mostly with haematological malignancies but also including 351 healthy donors have been successfully mobilized for autologous or allogeneic stem cell transplantation using biosimilar G- CSF (Zarzio TM: 1239 individuals; Ratiograstim TM/Tevagrastim TM: 653 individuals). A total of 740 patients with multiple myeloma, 491 with non-Hodgkin's lymphoma ( NHL), 150 with Hodgkin's lymphoma ( HL) and other diseases are included in this meta-analysis, as well as 161 siblings and 190 volunteer unrelated donors. For biosimilar and originator G- CSF, bioequivalence was observed for the yield of CD34+ stem cells as well as for the engraftment of the transplants. Conclusion Biosimilar G- CSF has equivalent effects and safety as originator G- CSF. [ABSTRACT FROM AUTHOR]

Background aims. Filgrastim and lenograstim are the standard granulocyte colony-stimulating factor (G-CSF) agents for peripheral blood stem cell mobilization (PBSC) in patients who undergo autologous stem cell transplantation. Methods. To assess whether biosimilars are effective, we conducted a single-center, prospective study that included 40 consecutive de novo multiple myeloma patients who received cyclophosphamide 4 g/m² per day plus biosimilar filgrastim G-CSF to mobilize PBSC. These patients were compared with a group of 37 patients matched for age, diagnosis, previous chemotherapy and mobilization who had been treated with originator G-CSF. The mean number of CD34+ cells/µL in the peripheral blood was 199.6 ± 207.4 in the biosimilar and 192.8 ± 154.7 in the originator group (P = 0.87). The median number of CD34+ cells/kg recipient collected was 11.5 ± 5.8 and 12.3 ± 5.3 in the biosimilar and originator groups, respectively (P = 0.51). The mobilization failure rate was 2.5% and 2.7% in the biosimilar filgrastim and originator filgrastim cohorts (P = NS), respectively. Results. Twenty-nine patients in the biosimilar group and 28 patients in the originator group underwent autologous transplantation. There were no statistically significant differences between the biosimilar and originator G-CSF cohorts in terms of hematopoietic recovery parameters and transplant-related toxicities. Conclusions. The efficacy of bio-similar G-CSF appears to be equivalent to the reference G-CSF. [ABSTRACT FROM AUTHOR]

Purpose: Granulocyte colony-stimulating factors (G-CSFs), filgrastim and lenograstim, are recognised to be useful in accelerating engraftment after autologous stem cell transplantation. Several forms of biosimilar non-glycosylated G-CSF have been approved by the European Medicines Agency, with limited published data supporting the clinical equivalence in peripheral blood stem cell mobilisation and recovery after autologous stem cell transplantation. Method: With the aim of comparing cost-effective strategies in the use of G-CSF after autologous stem cell transplantation, we retrospectively evaluated 32 patients consecutively treated with biosimilar filgrastim XM02 (Tevagrastim) and 26 with lenograstim. All patients received G-CSF (biosimilar or lenograstim) at a dosage of 5 mcg/kg/day subcutaneously from day 5 to absolute neutrophil count of 1500/mmc for three days. Results: The median time to absolute neutrophil count engraftment was 11 days for the filgrastim XM02 group and 12 days for the lenograstim group. As for platelets recovery, the median time was 12 days in both groups. The median number of G-CSF vials used for patients was 9.5 for Tevagrastim and 10.5 for lenograstim, reflecting a mean estimated cost of about 556.1 euros for Tevagrastim versus 932.2 euros for lenograstim (p < 0.001). The median days of febrile neutropenia were 1.5 and 1 for filgrastim XM02 and lenograstim, respectively. No adverse event related to the use of XM02 filgrastim was recorded. Conclusion: In our experience, filgrastim XM02 and lenograstim showed comparable efficacy in shortening the period of neutropenia after cytoreduction and autologous stem cell transplantation, with a favourable cost effect for filgrastim XM02. [ABSTRACT FROM AUTHOR]

The use of granulocyte colony stimulating factor (G-CSF) biosimilars for peripheral blood hematopoietic stem cell (PBSC) mobilization has stimulated an ongoing debate regarding their efficacy and safety. However, the use of biosimilar G-CSF was approved by the European Medicines Agency (EMA) for all the registered indications of the originator G-CSF (Neupogen (®) ) including mobilization of stem cells. Here, we performed a comprehensive review of published reports on the use of biosimilar G-CSF covering patients with hematological malignancies as well as healthy donors that underwent stem cell mobilization at multiple centers using site-specific non-randomized regimens with a biosimilar G-CSF in the autologous and allogeneic setting. A total of 904 patients mostly with hematological malignancies as well as healthy donors underwent successful autologous or allogeneic stem cell mobilization, respectively, using a biosimilar G-CSF (520 with Ratiograstim®/Tevagrastim, 384 with Zarzio®). The indication for stem cell mobilization in hematology patients included 326 patients with multiple myeloma, 273 with Non-Hodgkin's lymphoma (NHL), 79 with Hodgkin's lymphoma (HL), and other disease. 156 sibling or volunteer unrelated donors were mobilized using biosimilar G-CSF. Mobilization resulted in good mobilization of CD34+ stem cells with side effects similar to originator G-CSF. Post transplantation engraftment did not significantly differ from results previously documented with the originator G-CSF. The side effects experienced by the patients or donors mobilized by biosimilar G-CSF were minimal and were comparable to those of originator G-CSF. In summary, the efficacy of biosimilar G-CSFs in terms of PBSC yield as well as their toxicity profile are equivalent to historical data with the reference G-CSF.