Allogeneic Stem Cell Transplantation (Allo-SCT) in the Management of Advanced Waldenstrom’s Macroglobulinemia (WM).

Despite effectiveness of standard chemotherapy regimens, complete response is infrequent in WM patients and there is no cure. The role of Allo-SCT has not been extensively explored and the available data are limited. In this retrospective European multicenter study we report the outcome of 106 WM patients (69 male) who underwent an Allo-SCT between 1989 and 2005 and were reported to the EBMT Lymphoma Database. The median age at transplant was 49 years (21–65), and the median time from diagnosis to SCT was 34 months (5–310). The median number of treatment lines prior to allo-SCT was 3(1–10) and 19 patients had failed a prior autograft. Ten (10%) patients were in 1^st maximum response (MR), 35 (33%) in PR1, 29 (27%) in PR≥2 and 32 (30%) had refractory disease at the time of transplantation. Forty-four patients were treated with conventional (CT) conditioning protocols; [Cy/TBI n=24, Melphalan/TBI, n=6, BuCy n=14] and 62 with a reduced intensity protocol (RIC); [Fludarabine based regimen n=43, Low dose TBI/Cy n=19] With a median follow up of 31 months (3 to 169) 59 (56%) patients, are alive and free of disease. Forty-eight (45%) patients developed aGVHD [Grades I-II (n=34), Grades III-IV (n=14)] with no statistically significant difference between conventional and RIC groups. Five out of nine RIC patients developed aGVHD following the administration of donor lymphocytes for either residual disease or mixed chimerism. Sixteen patients (15%) developed limited and 11 (10%) extensive chronic GVHD. Seventeen (16%) patients relapsed at a median time of 8 (1–89) months after allo-SCT. Thirty-five (33%) patients died, 5 (5%) from disease relapse or progression and 30 (28%) from regimen toxicity. Non-relapse mortality rates were estimated of 30% and 33%, at 1 and 3 years, respectively, for the CT group, and 24% and 30% for the RIC group of patients. Relapse rates at 1 and 3 years were 10%, 12% for the CT group and 14% and 25% for the RIC. Progression free survival (PFS) rates were 60%, 54% and 54% at 1, 3 and 5 years for the CT and 61%, 44% and 39% for the RIC patients. Overall survival was 65%, 59% and 59% for the CT and 71%, 66% and 66% for the RIC at 1, 3 and 5 years, respectively. Multivariate analysis showed that chemorefractory disease at allo-SCT was associated with a significantly higher relapse rate [p<0.03; 95% CI 1.1–8.9] while the use of TBI in the conditioning regimen with a significantly lower relapse rate [p<0.02; 95% CI 1.1–9.3]. There were no differences in outcome when considering the intensity of the conditioning regimen. In conclusion, allo-SCT is a feasible and well-tolerated procedure in this group of elderly patients with advanced disease. In addition, relapse rate after the allogeneic procedure is low resulting in a good long-term outcome.