CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Clinical pathology abstracts editor: Deborah Sesok-Pizzini, MD, MBA, associate professor, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, and medical director, Blood Bank and Transfusion Medicine, Children’s Hospital of Philadelphia.
A benefit of HLA-haploidentical bone marrow transplant with post-transplant cyclophosphamide
Although allogeneic bone marrow transplantation can cure sickle cell disease, human leukocyte antigen-matched donors are difficult to find, and the toxicities of myeloablative conditioning prior to transplants are a major risk factor for morbidity and mortality in most adults. The authors developed for patients with sickle cell disease newer bone marrow transplant regimens using nonmyeloablative conditioning regimens and human leukocyte antigen (HLA)-haploidentical donors. They conducted transplants on 17 patients who had sickle cell disease—using 14 donors with a HLA-haploidentical match and three HLA-matched related donors. The regimen consisted of antithymocyte globulin, fludarabine, cyclophosphamide, total body irradiation, and graft-versus-host disease prophylaxis with post-transplantation high-dose cyclophosphamide, mycophenolate mofetil, and tacrolimus or sirolimus. The outcomes were positive for the majority of the patients, with 10 patients asymptomatic after a median followup of 711 days and six patients entirely off immunosuppression. Only one patient developed skin-only acute graft-versus-host disease, and the disease resolved without therapy. The authors concluded that nonmyeloablative conditioning with post-transplantation cyclophosphamide resulted in low-risk complications, even with haploidentical-related donors. Therefore, full donor chimerism was not required to improve symptoms of sickle cell disease in this cohort of patients. Patients with mixed chimerism also demonstrated improvement in hemolysis, pain, and transfusion needs. The authors concluded that these findings would make it feasible to identify more donors that can provide transplants to patients with sickle cell disease. However, the authors noted that continued graft failure, at 43 percent in their study, is a concern because it remains an obstacle in haploidentical pairs.
Bolanos-Meade J, Fuchs EJ, Luznik L, et al. HLA-haploidentical bone marrow transplantation with post-transplant cyclophosphamide expands the donor pool for patients with sickle cell disease [published online ahead of print September 6, 2012]. Blood. doi:10.1182/blood.2012.07.438408.
Correspondence: Dr. Javier Bolanos-Meade at fbolano2@jhmi.edu