Allogeneic Stem Cell Transplantation in Multiple Myeloma: One Center Experience of 86 Patients.

Abstract

The role of allogeneic stem cell transplantation (SCT) in the treatment of multiple myeloma (MM) is unclear. High transplant-related mortality has been regarded as a particular problem. At the Helsinki University Central Hospital 86 patients with MM have been treated with allogeneic SCT since 1995. The conditioning was at first myeloablative (MA). Since 1999 reduced intensity conditioning (RIC) after autologous SCT has been used in most cases, but a number of young patients with aggressive disease have been transplanted with MA conditioning. Of the patients 42 were male and 44 female. The median age at SCT was 50 (27–64) years. The median number of chemotherapy lines before allogeneic SCT was 1 (range 1–7). Prior autologous SCT had been performed to 55 patients. The median time from diagnosis to allogeneic SCT was 12 (4–168) months, and the time between autologous and allogeneic SCT 6 (2–146) months. At the time of allogeneic SCT 9 patients were in CR, 63 in PR, 4 had stable disease, and 10 progressive disease. 72 patients had a sibling donor: 68 were HLA-identical, one 1 antigen mismatch, 3 identical twins. 14 patients had an HLA-matched unrelated donor. The conditioning was MA in 32 and RIC in 54 patients. The MA conditioning consisted of Cy/TBI in 22, Mel/TBI in 3, and Treosulfan/Fld in 7 patients. RIC was the Seattle protocol (Fld/TBI 2 Gy) in 45, reduced Treosulfan/Fld in 8, and Fld/Cy in 1 patient. 26 patients received a BM graft and 60 patients a PB graft. As GVHD prophylaxis, 18 patients were given CsA/Mtx, 20 CsA/Mtx/MP, 45 CsA/MMF, and 3 nothing (identical twins). The median follow-up time from allogeneic SCT was 39 (2–136) months, 46 (7–136) months for the MA patients and 34 (2–92) months for the RIC patients, respectively. The OS was 50% at 61 months post SCT and there have been no deaths after this time-point. The median PFS was 31 months. After this time-point the disease has progressed in one case, at 90 months. Of the 32 MA patients 16 (50%) and of the 54 RIC patients 22 (41%) have achieved CR after SCT. The cumulative incidence of acute GVHD grade II-IV was 28%. The cumulative incidence of chronic GVHD was 72%, 58% in the MA and 83% in the RIC patients (p=0.074). The incidence of extensive chronic GVHD was significantly (p=0.012) higher in RIC than MA patients, 66% vs. 23%. There were no statistical differences in the incidence of acute or chronic GVHD by donor type (72 siblings/14 unrelated). The cumulative 100-day transplant related mortality was 4.5% and that of the whole follow-up time 14%. 26 patients have died. The cause of death was myeloma in 15, GVHD in 7, and infection in 4 patients. In conclusion, in the present material transplant-related mortality was low and the survival encouraging, supporting the use of allogeneic transplantation with curative aim in selected cases. Developing chemotherapy, given prior to transplantation, may improve the results.