Allogeneic Transplantation for Multiple Myeloma

Abstract

Autologous hematopoietic stem cell transplantation (HSCT) is currently considered part of the standard care in the management of patients with newly diagnosed multiple myeloma (MM). Autologous transplantation has extended overall survival and progression-free survival by 1–1.5 years compared to conventional dose chemotherapy in randomized clinical studies 1 – 3 in patients up to 65 years of age. Unfortunately, long-term survival for patients treated with autologous HSCT is rare, and virtually all patients relapse. Allogeneic (Allo-) HSCT can induce long-term molecular remission and is possibly the only curative treatment for MM based on the graft-versus-tumor (GVT) or graftversus-myeloma (GVM) effects mediated by the allogeneic donor immune cells, particularly donor T-cells. Advantages of allogeneic HSCT in comparison to autologous HSCT are a tumor-free stem cell source and the GVM effect. Current clinical research is trying to define the clinical outcomes of patients allocated to allogeneic transplantations based on the availability of human leukocyte antigen (HLA)-matched donor versus patients without a suitable donor who undergo one or two autologous transplantations. 4 , 5 Recent publications indicated that durable engraftment and less regimen-related toxicity can be obtained in allogeneic transplantation using reduced intensity conditioning (RIC) regimen that do not result in myeloablation. 6 – 8 Despite reduced early mortality, significant rates of graft-versus-host (GVH) disease and late relapse remain problems following RIC regimens, highlighting the need for novel strategies to enhance and target the GVM effect in allogeneic transplantation. This chapter will highlight the antigenic targets for GVM and review the clinical experience with donor leukocyte infusions, myeloablative transplants, nonmyeloablative conditioning regimens, and the use of tandem auto-allo transplants for this disease.