Randomized comparison of granulocyte colony-stimulating factor versus granulocyte-macrophage colony-stimulating factor plus intensive chemotherapy for peripheral blood stem cell mobilization and autologous transplantation in multiple myeloma

Abstract

Autologous peripheral blood stem cell transplantation for multiple myeloma offers higher response rates and improved survival compared with conventional chemotherapy. However, successful autografting requires effective cytoreduction and rapid hematologic reconstitution. We conducted a prospective randomized clinical trial to assess the efficacy of 2 cycles of priming chemotherapy with either granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) for peripheral blood stem cell mobilization followed by autologous transplantation. The major study end points were the comparative utility of G-CSF versus GM-CSF, the percentage of patients achieving complete response after transplantation, and overall and progression-free survival. Priming chemotherapy included cyclophosphamide (4 g/m2), mitoxantrone (8 g/m2 every day for 2 days), and dexamethasone (20 mg/m2 every 12 hours for 2 days) followed by randomization to either G-CSF or GM-CSF daily until completion of leukapheresis. Conditioning for transplantation included cyclophosphamide (75 mg/kg every day for 2 days) plus total body irradiation (165 cGy twice daily for 3 days), and patients received maintenance immunotherapy with interferon alpha. Seventy-two patients were randomized, and 64 underwent autologous transplantation. The median age at transplantation was 52 years, and the median time from diagnosis to transplantation was 10 months; 58% of the patients had received >4 cycles of pretransplantation chemotherapy. The median number of CD34+ cells obtained after mobilization was 16.4 x 10(6)/kg in the G-CSF arm versus 12.8 x 10(6)/kg in the GM-CSF arm (P = .8). Neutrophil recovery was faster in the G-CSF group after both cycle 1 (median, 13 days with G-CSF and 16 days with GM-CSF; P < .01) and cycle 2 (median, 13 days versus 17 days in the 2 groups, respectively; P = .03). Although platelet recovery was similar after cycle 1, platelet recovery to >100000/microL was notably faster in the G-CSF group both after cycle 2 and after transplantation (P = .03). Response and overall and disease-free survival were similar in both cohorts. Overall, 23% of the patients achieved a complete response after priming chemotherapy, which improved to 33% after transplantation. An additional 47% attained a partial response after transplantation, for a total response rate of 80%. With a median follow-up of 2 years (range, 0.7-8 years), the overall survival was 88% (95% confidence interval [CI], 80%-96%) at 1 year and 65% (95% CI, 51%-79%) at 3 years. Progression-free survival was 73% (95% CI, 62%-84%) at 1 year and 40% (95% CI, 26%-54%) at 3 years. Relapse or progressive disease was the most common cause of death (25 [83%] of 30 deaths). We conclude that mobilization with chemotherapy plus G-CSF versus GM-CSF results in similar CD34+ progenitor collections, even in patients exposed to multiple cycles of alkylator-based chemotherapy. Earlier neutrophil and platelet recovery was seen with G-CSF priming. Two cycles of priming chemotherapy plus autologous transplantation yields survival rates similar to those in published reports, including those using tandem transplantation.