Allogeneic hematopoietic cell transplantation for multiple myeloma

At the present time, allogeneic hematopoetic stem cell transplantation (AHSCT) is the only proven treatment for multiple myeloma (MM) that is potentially curative. This conclusion is based on observations of patients who have undergone AHSCT and are living disease-free for 5-15 years. While patients who receive either allogeneic or autologous stem cell transplants for MM have similar 3-5 year survival, only allograft recipients appear to enjoy long-term disease free survival. This is most likely due to an allogeneic graft-versus-myeloma effect, demonstrated most dramatically by complete responses observed after the simple infusion of donor lymphocytes for patients who have relapsed after a prior allograft. The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment modality. Complications are age-related and thus standard AHSCT is offered only to patients under age 55; further limiting the utility of this treatment. The challenge for clinical investigators will be to reduce the incidence of post-transplant complications for patients receiving AHSCT for MM. These strategies include the use of non-ablative conditioning regimens, the use of peripheral blood stem cells rather than bone marrow, graft engineering and targeted conditioning therapies such as bone-seeking radioisotopes. In one such approach, tandem autologous/non-ablative allogeneic transplants have been shown to result in relatively low mortality, high complete response rates and 1-year survivals of 81%. Further follow-up and randomized trials will help to define the utility of this strategy.