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.