Single Institution Experience with Two High-Dose Chemotherapy (HDC) Conditioning Regimens Prior to Autologous Stem Cell Transplant (ASCT) for Multiple Myeloma (MM).

HDC with ASCT has become a standard treatment for patients with MM. Based on the results of recent trials, the use of melphalan (MEL) 200mg/m² has emerged as the preferred HDC conditioning regimen, although research towards defining the optimal preparative regimen for these patients continues. We report our institution’s experience with two sequential patient cohorts receiving HDC regimens prior to ASCT as treatment for MM. From July 1992 through August 2003, 62 patients received the combination of high-dose busulfan (1 mg/kg orally every 6 hours for 14 doses on day −8 to −5), etoposide (60 mg/kg 36-hour continuous intravenous [IV] infusion on days −5 and −4) and cyclophosphamide (60 mg/kg/day IV on days −3 and −2) (BVC), and 48 patients received MEL 200 mg/m² as a single IV dose on day −2). Prior to conditioning, peripheral blood stem cells were mobilized with etoposide or cyclophosphamide followed by filgrastim (gCSF) given subcutaneously at 10 μg/kg/day. At least 5 x 10⁶ CD34+/kg ideal body weight was targeted for collection. Two patients in the BVC group had CD34+ cells harvested directly from bone marrow. In both groups, autologous stem cells were infused on day 0. Patients received aggressive supportive care measures including intravenous anti-emesis medications and analgesia as required, prophylactic antibiotics, blood product transfusion and filgrastim (gCSF) support. Patients treated with BVC and MEL were similar in age (median ages, 55 vs 58 years), MM subtype (IgG in BVC = 65%, IgG in MEL = 56%) and timing of transplant from diagnosis. Median time from diagnosis to transplant for BVC was 289 days (d), and for MEL was 287 d. 90% of BVC patients and 91% of MEL patients were receiving HDC/ASCT as second-line therapy. Whereas 39% of BVC patients and 58% of MEL patients had stage III disease, 30% of BVC patients and 23% of MEL patients were classified as having “progressive” or “refractory” disease at time of transplant. Median beta-2 microglobulin for BVC patients was 2.99 mg/dl and for MEL patients was 3.87 md/dl. Patients were similar in median length of hospitalization (BVC = 20 d vs MEL = 16 d), median duration of neutropenia (BVC = 9 d vs MEL = 10 d), and mdian duration of thrombocytopenia (BVC= 15 d vs MEL = 17 d). Toxicities of therapy were similar between groups, although there were two treatment related mortalities (TRM) in the BVC group (one attributed to infection, one to hepatic veno-occlusive disease). The median progression-free survival was similar between groups (BVC = 803 d vs MEL = 749 d, p > .05). The median overall survival (OS) for BVC pts was 1394 d while the median OS for MEL pts has not been reached to date (p>0.05). Our results indicate that MEL and BVC achieve similar long-term outcomes in patients with MM.