Peripheral Blood Stem Cell Mobilization and Engraftment after Autologous Stem Cell Transplantation with Biosimilar rhG-CSF

INTRODUCTION: Biosimilar versions of filgrastim [recombinant human granulocyte colony-stimulating factor (rhG-CSF)] are now widely available. To date, biosimilar rhG-CSF has demonstrated a comparable quality, safety and efficacy profile to the originator product (filgrastim [Neupogen((R))], Amgen Inc., CA, USA) in the prevention and management of neutropenia. Biosimilar rhG-CSFs have also been used to induce peripheral blood stem cell (PBSC) mobilization in patients undergoing autologous stem cell transplantation (AHSCT). The authors have examined the effectiveness of a biosimilar rhG-CSF (Zarzio((R)), Sandoz Biopharmaceuticals, Holzkirchen, Germany) in two retrospective studies across two medical centers in Hungary. METHODS: In Study 1, 70 patients with hematological malignancies scheduled to undergo AHSCT received chemotherapy followed by biosimilar rhG-CSF (2 x 5 mug) for facilitating neutrophil, leukocyte, and platelet engraftment. In study 2, 40 additional patients with lymphoid malignancies and planned AHSCT received chemotherapy followed by biosimilar rhG-CSF for PBSC mobilization. The effectiveness of treatment was assessed by the average yield of cluster of differentiation (CD) 34+ cells and the number of leukaphereses required. RESULTS: In Study 1 (patients undergoing AHSCT), the median age was 56 years and most patients were male (60%). The conditioning regimens were mainly high-dose melphalan (n = 41) and carmustine (BiCNU((R)), Bristol-Myers Squibb, NJ, USA), etoposide, cytarabine and melphalan BEAM (n = 21). Median times to absolute neutrophil and leukocyte engraftment were 9 (range 8-11 days) and 10 (8-12) days, respectively. Median time to platelet engraftment was 10.5 days (7-19 days). In Study 2, the patients' median age was 54 years and the majority (57.5%) were female. The median time interval between day 1 of mobilizing chemotherapy and first leukapheresis was 12 (9-27) days. In the autologous PBSC grafts, the median number of CD34+ cells harvested was 5.2 x 10(6)/kg (2.22-57.07 x 10(6)/kg). The median yield of CD34+ cells per leukapheresis product was 2.47 x 10(6)/kg. In total, 58 leukaphereses were performed in 40 successfully harvested patients. CONCLUSIONS: In line with previous studies with originator rhG-CSF, the findings of this study indicate that biosimilar rhG-CSF following AHSCT is effective and generally well tolerated in the engraftment setting. In addition, biosimilar rhG-CSF is comparable to the originator rhG-CSF in terms of kinetics of PBSC mobilization and yield of CD34+ cells. In conclusion, the authors have demonstrated that the use of biosimilar rhG-CSF is effective and safe in autologous PBSC mobilization and engraftment after AHSCT

Outcomes and costs of autologous stem cell mobilization with chemotherapy plus G-CSF vs G-CSF alone

Chemotherapy plus granulocyte colony stimulating factor (G-CSF) (C+G) and G-CSF alone are two of the most common methods of mobilizing CD34+ cells for autologous hematopoietic stem cell transplantation (AHSCT). In order to compare and determine real-world outcomes and costs of these strategies, we performed a retrospective study of 226 consecutive patients at 11 medical centers (64 lymphoma, 162 multiple myeloma), of whom 55% and 66% received C+G. Patients with C+G collected more CD34+ cells/day than G-CSF alone (lymphoma: average 5.51x10(6) cells/kg on day 1 vs. 2.92x10(6) cells/kg, p=0.0231; myeloma: 4.16x10(6) cells/kg vs. 3.69x10(6) cells/kg, p<0.00001) and required fewer days of apheresis (lymphoma: average 2.11 days vs. 2.96, p=0.012; myeloma: 2.02 vs. 2.83 days, p=0.0015), though nearly all patients ultimately reached the goal of 2x10(6) cells/kg. With the exception of higher rates of febrile neutropenia in myeloma patients with C+G (17% vs. 2%, p<0.05), toxicities and other outcomes were similar. Mobilization with C+G cost significantly more (lymphoma: median $10,300 vs.$7,300, p<0.0001; myeloma: $8,800 vs.$5,600, p<0.0001), though re-mobilization adds $6,700 for drugs alone. Our results suggest that while both C+G and G-CSF alone are effective mobilization strategies, C+G may be more cost-effective for patients at high risk of insufficient mobilization

Plerixafor for PBSC mobilisation in myeloma patients with advanced renal failure: safety and efficacy data in a series of 21 patients from Europe and the USA

We describe 20 patients with myeloma and 1 with primary amyloidosis from 15 centres, all with advanced renal failure, most of whom had PBSC mobilised using plerixafor following previous failed mobilisation by conventional means (plerixafor used up-front for 4 patients). For 15 patients, the plerixafor dose was reduced to 0.16 mg/kg/day, with a subsequent dose increase in one case to 0.24 mg/kg/day. The remaining six patients received a standard plerixafor dosage at 0.24 mg/kg/day. Scheduling of plerixafor and apheresis around dialysis was generally straightforward. Following plerixafor administration, all patients underwent apheresis. A median CD34+ cell dose of 4.6 × 106 per kg was achieved after 1 (n=7), 2 (n=10), 3 (n=3) or 4 (n=1) aphereses. Only one patient failed to achieve a sufficient cell dose for transplant: she subsequently underwent delayed re-mobilisation using G-CSF with plerixafor 0.24 mg/kg/day, resulting in a CD34+ cell dose of 2.12 × 106/kg. Sixteen patients experienced no plerixafor toxicities; five had mild-to-moderate gastrointestinal symptoms that did not prevent apheresis. Fifteen patients have progressed to autologous transplant, of whom 12 remain alive without disease progression. Two patients recovered endogenous renal function post autograft, and a third underwent successful renal transplantation. Plerixafor is highly effective in mobilising PBSC in this difficult patient group

Progenitor cell mobilisation - Cyclophosphamide, etoposide and G-CSF to mobilize peripheral blood stem cells for autologous stem cell transplantation in patients with lymphoma

We aimed to assess the effectiveness of cyclophosphamide, etoposide and G-CSF (C+E) to mobilize peripheral blood stem cells for autologous stem cell transplantation in patients with lymphoma. A matched cohort study was performed comparing patients mobilized with C+E to patients mobilized with cyclophosphamide and G-CSF (C alone). Patients were matched for disease, prior radiotherapy and a chemotherapy score reflecting the amount and type of prior chemotherapy. Thirty-eight consecutive patients mobilized with C+E were compared with 38 matched controls. C+E was equivalent to C alone in terms of numbers of patients achieving a minimum threshold of greater than or equal to2 x 10(6)/kg CD34(+) cells (82% vs 79%, P = 0.74). C+E was superior, however, in terms of total CD34(+) yield (6.35 vs 3.3 x 10(6)/kg, P < 0.01), achieving a target graft of greater than or equal to5 x 10(6)/kg (55% vs 34%, P = 0.04) and obtaining both a minimum (61% vs 32%, P < 0.01) and target (45% vs 13%, P < 0.01) graft in one apheresis. This superiority was largely confined to patients with lower chemotherapy scores. There was no difference in neutrophil and platelet recovery or transfusion requirements for those who subsequently received high-dose therapy and stem cell transplantation. Thus, C+E improves the efficiency of peripheral blood stem cell collection, but does not increase the number of patients who can proceed to transplantation. Most of the benefit of the regimen was confined to patients who had not received extensive prior therapy. Novel strategies are required to increase the collection efficiency of 'hard to mobilize' patients