Reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation

Chemotherapy and radiotherapy administered in preparation for allogeneic hematopoietic progenitor cell transplantation serve the dual role of providing antitumor activity as well as immunosuppression to prevent graft rejection. Conditioning regimens were initially designed to provide dose-intense therapy in order to overcome tumor resistance. These forms of transplants, referred to as ablative regimens, often result in significant extramedullary toxicity, limiting its applicability to younger, fitter patients. Reduced-intensity conditioning (RIC) transplants are a direct result of an understanding of the immunotherapeutic potential of the donated hematopoietic stem cells. These forms of transplants administer chemoradiotherapy with the intent of allowing for donor cell engraftment with less of an emphasis on dose intensity. In so doing, treatment-related mortality has been reduced, and older-aged patients and those with co-morbidities are now frequently offered this therapy. In the decade since its creation, RIC transplantation has changed the spectrum of patients with malignancies who may benefit from this therapy. For the first time, transplant patients are becoming more representative of the populations most at risk for diseases requiring this therapy. This article reviews the science behind RIC transplants and provides a concise summary of the current body of evidence for the major indications for which it is most commonly employed. The data presented will demonstrate that age should no longer be the sole deciding factor for referral for allogeneic transplant.