A conditioning regimen comprising busulfan, fludarabine, and thymoglobulin may be associated with increased efficacy of bone marrow transplantation (BMT) in adults with sickle cell disease (SCD), according to a study published in the American Journal of Hematology.
In a pilot investigation, 22 patients with SCD (median age, 22.5 years) underwent BMT. All patients received marrow from a related (17 patients) or unrelated (5 patients) human leukocyte antigen (HLA)-matched donor.
Prior to undergoing transplantation, patients received a reduced toxicity conditioning regimen consisting of 13.2 mg/kg busulfan given daily, intravenously, on days -8 to -5; 35 mg/m2 fludarabine given daily, intravenously, on days -7 to -3; and doses of thymoglobulin ranging from 0.5 mg/kg to 1.5 mg/kg given daily, intravenously, on days -6 to -2.
Patients also received methotrexate and tacrolimus or cyclosporine for graft-versus-host disease (GVHD) prophylaxis. Primary endpoint was 1-year event-free survival (EFS) of 70% or greater.
At 1 year after BMT, EFS was 86% and overall survival was 91%; at 3 years after BMT, EFS was 82%. Patients demonstrated significant improvements in physical function (P =.044) and pain interference (P =.006).
There were 2 patient deaths during the course of the study. One patient developed hemolysis and severe cytopenia and later received a second BMT. Overall, 10 patients developed acute GVHD (4 patients) or chronic GVHD (6 patients).
The researchers concluded that this conditioning regimen was well tolerated and efficacious in adults with SCD. A large multicenter trial (ClinicalTrials.gov Identifier: NCT02766465) in which the researchers plan to use this regimen is now underway to compare BMT with the standard of care in individuals without a suitably matched donor.
1. Krisnamurti L, Neuberg DS, Sullivan KM, et al. Bone marrow transplantation for adolescents and young adults with sickle cell disease: results of a prospective multicenter pilot study [published online January 13, 2019]. Am J Hematol. doi: 10.1002/ajh.25401