Reduced-intensity conditioning (RIC) regimens have the potential to decrease toxicities related to hematopoietic stem cell transplantation (HCT) in patients with sickle cell disease (SCD) and thus make HCT a more acceptable therapeutic option for this group of patients. We report the results of 7 patients enrolled on a study to evaluate safety and efficacy of HCT using bone marrow from an HLA matched sibling donor following an RIC regimen for patients with high-risk SCD. The conditioning regimen consisted of busulfan, fludarabine, equine antithymocyte globulin, and total lymphoid irradiation with shielding of the liver, lungs, heart, and gonads on day 1. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. The regimen was well tolerated, and all patients had hematopoietic recovery. Six of 7 patients are stably engrafted off immunosuppression and without sickle cell-related symptoms at 2 to 8.5 years after HCT. Consistent with the complete resolution of SCD related symptoms observed in the 6 engrafted patients, erythropoiesis of complete or predominantly donor origin was detected by red blood cell-specific chimerism assays, despite their having persistent mixed chimerism in the mononuclear and lymphoid compartments. These findings demonstrate the curative potential of allogeneic HCT after an RIC regimen in patients with SCD.
Bibliographical noteFunding Information:
We would like to acknowledge the dedicated work and support from the clinical transplant teams at the Children's Hospital of Pittsburgh, Pittsburgh, PA, University of Minnesota, Minneapolis, MN, and the University of Alabama, Birmingham AL. We thank Carol Schwartz, Betty Leef, and Mary Campbell for these excellent help in sample procurement, and expert technical assistance from Phil Zorich. This work is funded in part by the Cooleys Anemia Foundation (L.K.) and Doris Duke Charitable Foundation (C.J.W.). Finally, we thank Joe Antin and Frank Bunn for insightful discussions and their critical reading of the manuscript.
- Allo transplantation
- Clinical results in inherited disorders
- Conditioning regimen
- Marrow and stem cell transplantation
- Red cells, anemia-clinical
- Sickle cell anemia