Progress in allogeneic transplantation for multiple myeloma

Allogeneic hematopoietic stem cell transplantation to treat multiple myeloma has been attempted since the early 1980s. The original conditioning regimen including high-dose total body irradiation (TBI) plus cyclophosphamide was myeloablative and associated with a relatively low relapse/progression rate, but high transplant-related mortality and no obvious improvement in progression-free survival or overall survival. Some risk groups may benefit from this transplant modality and occasional patients may be cured, but due to the high-transplant-related mortality it is mainly abandoned. Reduced intensity conditioning (RIC), non-myeloablative allogeneic transplantation reduces transplant-related mortality significantly when compared with myeloablative conditioning, but the relapse/progression rate is somewhat higher. However although the treatment-related mortality is higher than after autologous transplantation, the progression-free and overall survival was better or tended to be better in three of five prospective trials comparing tandem autologous/RIC allogeneic transplantation to single or tandem autotransplantation due to lower relapse/progression rate. Adding donor lymphocyte infusions post-transplant, new drugs like bortezomib, thalidomide, lenalidomide or pomalidomide pre- and/or post-transplant, and more specific antimyeloma cell therapy like NK cells post-transplant, may in future studies prove to improve results.