Multicyclic, dose-intensive chemotherapy supported by hemopoietic progenitors in refractory myeloma patients

Attempts to increase dose intensity have been hampered by hematologic toxicity. To address this issue, we designed a study to determine whether the reinfusion of PBPC significantly reduces the toxicity of multicyclic dose-intensive chemotherapy. Thirty refractory patients, median age 63, received CY 3 g/m2 plus melphalan 60 mg/m2 followed by PBPC and G-CSF (CM regimen). CY (at day 0) and G-CSF were used to mobilize PBPC harvested by a single leukapheresis at day 10. Melphalan was infused at day 11. PBPC were kept unprocessed at 4 degrees C for 48 h and reinfused at day 12. This regimen was repeated three times every 6 months. Outcomes were compared with those of 30 similar patients treated with melphalan 30 mg/m2 followed by G-CSF only, and repeated every 2 months for a total of six cycles. In patients receiving CY plus melphalan followed by PBPC reinfusion, the median duration of neutropenia (ANC < 500/microliters) and thrombocytopenia (platelets < 2500 microliters) was only 5 and 2 days respectively, and did not increase after the subsequent courses. Hematologic toxicity was quite similar to that observed after melphalan 30 mg/m2 plus G-CSF. The CM regimen was followed by 30% complete remission and 86% response > 50%, melphalan 30 mg/m2 by no complete remissions and 38% response > 50%. Patients receiving CM regimen showed a longer progression-free survival (22 vs 10 months, P < 0.01). The dose intensity of melphalan can be doubled by reinfusing PBPC without increasing toxicity. The combination of CY and melphalan followed by PBPC improves response rate and outcome when compared to low-dose melphalan.