title: HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease.
abstract: 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 nonmyeloablative bone marrow transplantation platform using related, including HLA-haploidentical, donors for patients with sickle cell disease. The regimen consisted of antithymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation, and graft-versus-host disease prophylaxis with posttransplantation high-dose cyclophosphamide, mycophenolate mofetil, and tacrolimus or sirolimus. After screening 19 patients, we transplanted 17, 14 from HLA-haploidentical and 3 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 6 patients are off immunosupression. Only 1 patient developed skin-only acute graft-versus-host disease that resolved without any therapy; no mortality was seen. Nonmyeloablative conditioning with posttransplantation 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.
authors.affiliation: Hematologic Malignancies and Bone Marrow Transplantation Program, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and Johns Hopkins University School of Medicine, Baltimore, MD 21231-1000, USA. fbolano2@jhmi.edu
authors.forename: Javier
authors.initials: J
authors.lastname: Bolaños-Meade
authors.forename: Ephraim J
authors.initials: EJ
authors.lastname: Fuchs
authors.forename: Leo
authors.initials: L
authors.lastname: Luznik
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Lanzkron
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Gamper
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Jones
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brodsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000276:immunology / Q000628:therapy*; D016026:Bone Marrow Transplantation / Q000379:methods*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D006648:Histocompatibility / Q000502:physiology; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors / Q000600:supply & distribution*; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide