The current status of reduced-intensity allogeneic hematopoietic stem cell transplantation for multiple myeloma

Of all the treatment modalities employed to control multiple myeloma, only allogeneic hematopoetic stem cell transplantation is potentially curative, due in large part to a graft-versus-myeloma (GVM) effect. Whereas patients who receive either allogeneic or autologous stem cell transplants for multiple myeloma have similar 3–5-year survival, only allograft recipients appear to enjoy long-term disease-free survival. High transplant-related mortality (TRM) associated with allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative modality. This high mortality has been the major impetus for exploration of reduced intensity conditioning (RIC) regimens designed to allow engraftment of allogeneic stem cells. With follow-up now extending to 7 years, it is clear that when compared to myeloablative transplants, RIC allografts are associated with lower TRM; however, reduced mortality comes at a cost of higher rates of disease progression and relapse. Strategies designed to improve the therapeutic index of allografts include the use of more intensive, yet still non-myeloablative conditioning regimens, tandem autologous plus RIC allografts, peripheral blood cells rather than bone marrow, graft engineering to improve the GVM activity while reducing graft-versus-host disease, post-transplant maintenance and targeted conditioning therapies such as bone-seeking radioisotopes.