Outcome of allogeneic hematopoietic stem cell transplantation on diamond-blackfan anemia using busulfan-based myeloablative regimen

Abstract

Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is the only known curative option for hematologic manifestations of Diamond-Blackfan anemia (DBA) as a rare inherited bone marrow failure syndrome. This treatment may be considered for DBA patients with corticosteroid-resistance, transfusion dependence, and/or progression to severe aplastic anemia or myelodysplastic syndrome (MDS)/ Acute myleloid leukemia (AML). In this prospective study, 10 pediatric DBA patients (age < 15 years) who underwent allo-HSCT from HLA-matched donors using non-TBI myeloablative conditioning regimen (intravenous busulfan and cyclophosphamide ± antithymocyte globulin) during September 2010 to February 2014 are reported. For Graft versus Host Disease (GvHD) prophylaxis cyclosporine A. and a short course of methotrexate were administered. Except one patient who received transplantation from his sibling cord blood, engraftment occurred in all the other patients (9 out of 10) with full donor chimerism (> 95%). The median neutrophil and platelet engraftment times were 11 (range, 10-13) days and 23 (range, 15-50) days, respectively. Acute GvHD developed in 7 patients. After a median follow-up of 53.3 months, 8 patients are still alive, of whom 7 patients are disease-free. The other two patients died due to grade III-IV acute GvHD. Our data suggests that allo-HSCT using busulan-based non-TBI myeloablative conditioning regimen could be a long-term effective treatment for DBA patients. Early transplantation especially before having multiple transfusions leading to iron overload, particularly from an HLA-matched sibling donor would be associated with favorable outcomes.