Efficacy of Diverse High-Dose Regimens Followed by Autologous Peripheral Blood Stem Cell Transplantation in Consecutive Multiple Myeloma Patients: A Single Center Analysis over a 12 Year Period.

Over the last years, high-dose (HD) chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) has emerged as one very effective approach to improve the outcome in multiple myeloma (MM) patients (pts). HD- regimens in MM have been Busulfan and Cyclophosphamide (Bu/Cy) and HD-Melphalan (MEL), with or without total body irradiation (TBI). In this analysis, we analyzed the efficacy of different HD-regimens in consecutive MM (pts) receiving an auto-PBSCT at our institution between 8/1992 and 1/2005. Within these 12.5 years, 120 MM pts (68 male, 52 female) received an auto-PBSCT. Their median age was 56 (27–74) years. According to Durie &Salmon (DS), stage I, II and III disease prior to PBSCT were observed in 5 (4%), 30 (25%) and 85 pts (71%), respectively. Bu/Cy was used until 1997, TBI/MEL between 1997 and 1999, and MEL alone thereafter. The respective HD-regimens consisted of Bu/Cy (Bu 16mg/kg; Cy 120mg/kg) in 15 pts (12.3%), TBI/MEL (10 Gy; MEL 140 mg/m2) in 16 pts (13.1%) and MEL (200mg/m2) in 89 pts (73.0%). The median OS of all MM pts after auto-PBSCT in our analysis was 59.5 months. The therapy related mortality (d0 – d+100 after PBSCT) was 0% (0/15) for Bu/Cy, 3.4% (3/89) for MEL alone and 6.3% (1/16) for TBI/MEL. Main Bu/Cy side effects were infections (n=4), pulmonary fibrosis (n=2), renal failure (n=1) and VOD (n=1). Infections, mostly fever of unknown origin, were observed in the MEL and TBI/MEL group in 68/89 and 15/16 pts, respectively, however in none, pulmonary fibrosis, renal failure or VOD occurred. Comparing Bu/Cy- vs. MEL-conditioning in terms of OS, Bu/Cy prolonged OS in some pts (77.2 vs. 55.6 months, p=0.12), however, this difference failed to be of statistical significance. Our analysis on the influence of TBI on MEL-conditioning revealed no advantage for the combination-therapy (55.6 (+TBI) vs. 59.5 months (−TBI)), which confirms previous studies, also show no benefit for the addition of TBI. In conclusion, our data verify that comparable remission and OS rates can be obtained with less toxic conditioning regimens in MM, such as MEL200 alone, thereby significantly reducing therapy-related side effects. Since auto-PBSCT is an effective treatment option also for elderly and frail MM pts, choosing the best conditioning regimen is important and should improve the treatment outcome in MM further. Current studies are assessing the use of tandem-transplantations and novel anti-MM-agents, such as Bortezomib, Revlimid, Thalidomide and others, before, with and after high-dose regimens. These treatment concepts make highly effective but less toxic conditioning regimens imperative for auto- and allo-transplantations.