HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease

Hematologic Malignancies and Bone Marrow Transplantation Program, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of Medicine, Baltimore, MD, United States
Blood (Impact Factor: 10.45). 09/2012; 120(22). DOI: 10.1182/blood-2012-07-438408
Source: PubMed


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.

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Available from: Robert Brodsky, Jul 28, 2014
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    • "Despite success in small and now large animal models translation to clinical application remains challenging. In addition to the combined kidney and bone marrow transplantation studies reported by several centers [25, 26], recent work by Bolaños-Meade et al. [79] in the field of HLA mismatched bone marrow transplantation demonstrates progress toward establishment of chimerism across MHC barriers with a low incidence of GvHD suggesting that the goal of inducing VCA tolerance with mixed chimerism remains highly possible. In this paper we have reviewed a number of adjuvants to the mixed chimerism approach, which appear to have the potential to enhance engraftment and to mitigate complications such as GvHD. "
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