Unrelated Donor Hematopoietic Stem Cell Transplantation for Sickle Cell Disease

Abstract

Successful outcomes in children with sickle cell disease after matched sibling donor (MSD) transplantation are encouraging. Overall and event-free survival rates are >90%, disease symptoms such as pain improve over time, and neurologic and pulmonary functions stabilize. These outcomes support investigation of unrelated donor (URD) transplantation as an alternative given the paucity of human leukocyte antigen (HLA)-matched siblings (approximately 18%). In the MSD setting, outcomes are better when transplants are performed in the young (<16 years), as graft versus host disease (GVHD) and mortality risks increase with age. A number of URD hematopoietic stem cell transplantation (HSCT) trials are underway in children, fewer in adults. Early outcomes described after URD transplants have identified higher risks of rejection, GVHD, and mortality albeit in higher magnitude in some reports. This has triggered a second generation of URD HSCT trials focused on improving safety utilizing unrelated donor stem cell sources, new conditioning regimens, modern GVHD prophylaxis, and specific supportive care measures for known SCD-related problems. These trials typically are important because URD HSCT is undertaken typically after the disease has proved to be severe, i.e., generally in older children where transplant risks are higher. It is imperative that transplant methods continue to improve so results can mirror those after MSD transplants. This chapter describes indications for alternative donor HSCT, current status of this field of investigation, and future directions. URD HSCT, since investigational, should be performed in the context of well-planned clinical trials that aim to improve upon previous experience and track safety and success.