Allogeneic haematopoietic cell transplantation for multiple myeloma: Reducing transplant-related mortality while harnessing the graft-versus-myeloma effect

Allogeneic haematopoietic cell transplantation (allo-HCT) provides effective therapy for patients with various haematological malignancies. In multiple myeloma (MM) this approach can induce response rates in 35-75% of patients. However, the outcome is hampered by high rates of treatment-related mortality (TRM). Reduced intensity conditioning to lower TRM has been successfully applied. The fact that previous clinical reports have documented graft-versus-myeloma (GVM) activity without graft-versus-host disease (GVHD) suggests that at least two distinct immunocompetent cell populations mediating GVHD and/or GVM may exist. Further characterization of effectors after allo-HCT and their targets may help to clarify the immune response that mediates the GVM effect. This review considers the clinical results with myeloablative and reduced intensity conditioning prior to allo-HCT for MM, with emphasis on attempts to prevent GVHD while preserving the GVM effect. Strategies including donor lymphocyte infusions as part of the allogeneic protocol and antigenic targets for GVM effect are reviewed.