Recombinant human granulocyte and granulocyte–macrophage colony-stimulating factor (G-CSF and GM-CSF) administered following cytotoxic chemotherapy have a similar ability to mobilize peripheral blood stem cells

Abstract

Summary:The availability of hematopoietic growth factors has greatly facilitated the mobilization and collection of peripheral blood stem cells (PBSC). It was the aim of this double-blind study to compare the PBSC-mobilizing efficacy of recombinant human G-CSF and GM-CSF when administered post-chemotherapy. Twenty-six patients with relapsed Hodgkin's disease were included in the study. Their median age was 31 years (range, 22-59) and 14 patients were males and 12 were females. Patients were pretreated with a median of eight cycles of cytotoxic chemotherapy, while 18 patients had undergone extended field irradiation. The patients received dexamethasone 24 mg days 1-7, melphalan 30 mg/m 2 day 3, BCNU 60 mg/m 2 day 3, etoposide 75 mg/m 2 days 4-7, Ara-C 100 mg/m 2 twice daily days 4-7 (Dexa-BEAM). Twelve patients were randomized to receive 5 g/kg/day G-CSF and 14 patients to receive 5 g/kg/day GM-CSF, both administered subcutaneously starting on day 1 after the end of Dexa-BEAM. Primary endpoints of the study were the number of CD34 + cells harvested per kg body weight on the occasion of six consecutive leukaphereses and the time needed for hematological reconstitution following autografting. Twenty-one patients completed PBSC collection, and six patients of the G-CSF group and nine of the GM-CSF group were autografted. No difference was observed with respect to the median yield of CFU-GM and CD34 + cells: 32.5 × 10 4 /kg vs 31.3 × 10 4 /kg CFU-GM, and 7.6 × 10 6 /kg vs 5.6 × 10 6 /kg CD34 + cells, for G-CSF and GM-CSF, respectively (U test, P = 0.837 and 0.696). High-dose chemotherapy consisted of cyclophosphamide 1.7 g/m 2 days 1-4, BCNU 150 mg/m 2 days 1-4, etoposide 400 mg/m 2 days 1-4. All patients transplanted with more than 5 × 10 6 CD34 + cells/kg had a rapid platelet recovery (20 × 10 9 /l) between 6 and 11 days and neutrophil recovery (0.5 × 10 9 /l) between 9 and Correspondence: Dr S Hohaus, Department of Internal Medicine V, University of Heidelberg, Hospitalstr. 3, 69115 Heidelberg, Germany Received 9 April 1998; accepted 9 June 1998 16 days, while patients transplanted with less than 5 × 10 6 /kg had a delayed reconstitution, regardless of the kind of growth factor used for PBSC mobilization. In conclusion, our data indicate that in patients with Hodgkin's disease G-CSF and GM-CSF given after salvage chemotherapy appear to be not different in their ability to mobilize PBSC resulting in a similar time needed for hematological reconstitution when autografted following high-dose therapy.

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

“…The total number of progenitors collected, and median time to platelet and neutrophil engraftment, were similar for both groups. A number of chemotherapy-based mobilizing regimens has been reported in lymphoma patients, [32][33][34][35] however, only one is a randomized comparison to cyclophosphamide alone. 32 That trial compared ifosfamide 10 g/m 2 and GM-CSF to cyclophosphamide 4 g/m 2 and GM-CSF and reported similar CD34 + yields, but improved neutrophil engraftment and less toxicity with cyclophosphamide.…”

Mobilization of peripheral blood stem cells following myelosuppressive chemotherapy: a randomized comparison of filgrastim, sargramostim, or sequential sargramostim and filgrastim

“…However, one randomized trial compared filgrastim to molgramostim in 26 patients with Hodgkin's disease receiving MC. 16 Twenty-one patients completed PBSC collections and there were no differences in CD34 + cell yields or toxicities between the two groups. 16 Bregni et al, 18 in a non-randomized trial, compared filgrastim to molgramostim administered by continuous intravenous infusion in 49 patients with malignant lymphoma receiving cyclophosphamide 7 g/m 2 .…”

“…16 Twenty-one patients completed PBSC collections and there were no differences in CD34 + cell yields or toxicities between the two groups. 16 Bregni et al, 18 in a non-randomized trial, compared filgrastim to molgramostim administered by continuous intravenous infusion in 49 patients with malignant lymphoma receiving cyclophosphamide 7 g/m 2 . 18 These investigators found more rapid recovery of neutrophils following filgrastim (P = 0.01), more rapid recovery of platelets following molgramostim (P = 0.01), and more CD34 + cells/kg/apheresis following molgramostim (the latter difference not being statistically significant, P = 0.132).…”

“…16,18 Filgrastim has been compared to sargramostim or the combination of sargramostim and filgrastim in normal individuals. 13,[37][38][39] These studies demonstrated that filgrastim alone or sequential sargramostim and filgrastim mobilized more CD34 + cells than sargramostim alone in normal persons.…”

“…Sargramostim is a glycosylated form of rHuGM-CSF derived from yeast and marketed in the USA [12][13][14][15] and molgramostim is an unglycosylated form of rHuGM-CSF derived from Escherichia coli and only available for experimental use in the USA. [16][17][18][19][20][21][22][23][24] It has not been determined in randomized prospective trials whether there are major differences between myeloid growth factor regimens and CD34 + cell yields and morbidity following myelosuppressive chemotherapy (MC). There are reports of harvesting PBSC with MC followed by filgrastim, [4][5][6][7][8][9][10][11]25 sargramostim 14,15,26 or the combination of sargramostim and filgrastim, 12 but there have been no prospective, randomized studies comparing relative effectiveness.…”