MULTICYCLIC, DOSE-INTENSIVE CHEMOTHERAPY SUPPORTED BY HEMATOPOIETIC 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 whet her the reinfusion of PBPC significantly reduces the toxicity of multi cyclic dose-intensive chemotherapy, Thirty refractory patients, median age 63, received CY 3 g/m(2) plus melphalan 60 mg/m(2) followed by PB PC and G-CSF (CM regimen), CY (at day 0) and G-CSF were used to mobili ze PBPC harvested by a single leukapheresis at day 10, Melphalan was i nfused at day 11, PBPC were kept unprocessed at 4 degrees C for 48 h a nd reinfused at day 12, This regimen was repeated three times every 6 months, Outcomes were compared with those of 30 similar patients treat ed with melphalan 30 mg/m(2) followed by G-CSF only, and repeated ever y 2 months for a total of six cycles, In patients receiving CY plus me lphalan followed by PBPC reinfusion, the median duration of neutropeni a (ANC <500/mu l) and thrombocytopenia (platelets <25000/mu l) was onl y 5 and 2 days respectively, and did not increase after the subsequent courses, Hematologic toxicity was quite similar to that observed afte r melphalan 30 mg/m(2) plus G-CSF, The CM regimen was followed by 30% complete remission and 86% response >50%, melphalan 30 mg/m(2) by no c omplete remissions and 38% response >50%, Patients receiving CM regime n showed a longer progression-free survival (22 vs 10 months, P < 0.01 ), The dose intensity of melphalan can be doubled by reinfusing PBPC w ithout increasing toxicity, The combination of CY and melphalan follow ed by PBPC improves response rate and outcome when compared to low-dos e melphalan.