Stem cell factor (SCF) for hematopoietic stem cell (HSC) mobilization: Results of the randomized IFM 99-01 trial.

INTRODUCTION: In multiple myeloma, the usual mobilization protocol is toxic because of the use of cyclophosphamide. Several studies showed the interest of SCF. OBJECTIVE: To compare two mobilization protocols: endoxan 4g/m2 + G-CSF 5μg/kg/j (arm A) versus G-CSF 10μg/kg/j + SCF 25μg/kg/j (arm B) in a prospective, open and, randomized trial. PATIENTS AND METHODS: the studied criteria were the quality of the cell collections (objective > 5.106 CD34+ cells into 2 cytapheresis), the toxicity of the mobilization and graft phases, as well as the post-graft hematopoietic reconstitution. Multiple myeloma patients, less than 65 years old, with 0 or 1 risk factor (ß2microglobulin > 3 mg/L or chromosome 13 deletion) and who have a response ≥ 50% after 3 cures of VAD were included. After a fourth cure of VAD each patient was planed to receive a tandem transplant (IFM 99-02 trial). RESULTS: 150 patients (pts) were included and 138 were eligible (arm A = 67 pts, arm B = 71 pts). Pts and disease characteristics were similar in each arm. The objective of HSC collection was obtained with 92% pts in arm A and 81% pts in arm B (non significant). The total number of CD34+ cells collected were similar: 16.106 CD34+/kg (arm A) versus 15.106 CD34+/kg (arm B). Toxicity of HSC mobilization procedure was significantly different: duration of neutropenia < 500/mm3 (8 days in arm A versus 0 days in arm B, p<0.00001), duration of thrombopenia < 50 000/mm3 (5 days in arm A versus 0 days in arm B, p<0.0001), use of antibiotherapy (43% pts in arm A versus 9% pts in arm B, p<0.00001). 31% pts receiving SCF had local erythema at injection point. One pts experienced a grade 3 allergy in arm B. Hematopoietic reconstitution after first graft (high dose Melphalan 140 mg/m2, G-CSF at day 7) was not significantly different in either arm: duration of neutropenia < 500/mm3 (8 days in arm A versus 10 days in arm B), duration of thrombopenia < 50 000/mm3 (7.5 days in arm A versus 9 days in arm B), number of red blood cells units transfusions (1.5 versus 1.5). The 36 months overall survival probability was not significantly different with HDC mobilization (64%) versus SCF + G-CSF mobilization (87%). CONCLUSION: In myeloma patients, HSC mobilization with SCF + G-CSF is as effective as HDC + G-CSF, and gives very significant lower toxicities.