Reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) can result in reliable donor engraftment, relatively low treatment-related mortality, and sustained remissions in the treatment of multiple myeloma. However, substantial cytoreduction pre-allografting is often necessary because of a variable graft-versus-myeloma effect. The use of RIC allogeneic HSCT immediately after autologous HSCT provides a temporal separation between tumor reduction by high-dose chemotherapy and the graft-versus-myeloma effect. There are currently a number of prospective trials attempting to address the issue of whether this strategy leads to decreases in relapse and/or improvement in overall survival as compared with double autologous transplants. Unfortunately, similar to autografting, relapse remains the major cause of treatment failure after RIC allogeneic HSCT. To improve treatment results with allografting, consideration should be given to incorporating immunomodulatory drugs and targeted treatments to enhance pretransplantation remission status, as posttransplantation maintenance therapy, or in combination with donor lymphocyte infusions for refractory or relapsed disease. Studies exploring these strategies are ongoing.
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