Allogeneic marrow transplantation can cure sickle cell disease; however, HLA-matched donors are difficult to find, and the toxicities of myeloablative conditioning are prohibitive for most adults with this disease. We developed a non-myeloablative bone marrow transplantation platform using related, including HLA-haploidentical, donors for patients with sickle cell disease. The regimen consisted of anti-thymocyte globulin, fludarabine, cyclophosphamide and total body irradiation, and graft-versus-host disease prophylaxis with post-transplantation high dose cyclophosphamide, mycophenolate mofetil and tacrolimus or sirolimus. After screening 19 patients, we transplanted 17, 14 from HLA-haploidentical and three from HLA-matched related donors. Eleven patients engrafted durably. With a median follow up of 711 days (minimal follow up 224 days), 10 patients are asymptomatic, and six patients are off immunosupression. Only one patient developed skin-only acute graft-versus-host disease that resolved without any therapy, no mortality was seen. Non-myeloablative conditioning with post-transplantation high dose cyclophosphamide expands the donor pool making marrow transplantation feasible for most patients with sickle cell disease and is associated with a low risk of complications, even with haploidentical related donors. Graft failure, 43% in haploidentical pairs, remains a major obstacle, but may be acceptable in a fraction of patients if the majority can be cured without serious toxicities.
- Submitted July 2, 2012.
- Accepted August 20, 2012.
- Copyright © 2005 American Society of Hematology