Future directions in transplantation for aplastic anemia

Abstract Treatment algorithms for severe aplastic anemia (SAA) are evolving. A hematopoietic cell transplant (HCT) from a matched sibling donor is preferred for younger patients with SAA, whereas immunosuppressive treatment (IST) has traditionally been recommended for older patients. Because of the toxicity and risk associated with HCTs from alternative donors (ie, matched unrelated donors, haploidentical donors, or umbilical cord blood units), this approach has generally been reserved for patients who have experienced relapse after IST or have proved refractory to it. However, the recent development of reduced-toxicity conditioning regimens and the use of posttransplant cyclophosphamide as prophylaxis for graft-versus-host disease have significantly reduced the risk of morbidity and mortality after HCT. These changes have also expanded the pool of donors such that alternative donors are now increasingly being used for HCTs for patients with SAA. With the use of these novel HCT regimens and improved supportive care practices, overall survival and disease-free survival after HCT have improved over the last few decades, and disease-free survival after HCT may now be superior to that after IST. Several ongoing clinical trials are evaluating the use of matched unrelated donors and have expanded the use of haploidentical donors in the up-front setting for treatment-naive patients, thereby challenging the equipoise that has existed in this field for decades. These advances may usher in a paradigm shift in the management of SAA in the coming years.