Fludarabine-based conditioning for allogeneic transplantation in adults with sickle cell disease

Although allogeneic transplantation can be curative for patients with sickl e cell disease, the toxicity of conditioning regimens has precluded its use in adults with significant end-organ damage. Newer conditioning regimens h ave been developed that are less toxic and that may broaden the applicabili ty of allogeneic transplantation in this disorder. We report two adults wit h end-stage sickle cell disease, who underwent allogeneic transplantation f rom an HLA-identical sibling donor after conditioning with fludarabine/melp halan and ATG, Both patients had been extensively transfused and one had mu ltiple RBC antibodies. One of the patients also had end-stage renal disease , and was dialysis dependent. Engraftment occurred promptly in both patient s. Both achieved 100% donor chimerism and both were free of pain crises aft er transplant. The first patient died of a respiratory failure related to c hronic graft-versus-host disease (GVHD) on day 335 after transplantation. T he second patient developed severe gastro-intestinal GVHD and TTP and died on day 147 after transplantation. Conditioning with fludarabine/melphalan a nd ATG followed by allogeneic stem cell transplantation resulted in prompt and reliable engraftment in adults with end-stage sickle cell disease. The incidence of severe GVHD was unacceptably high and may be related to the et hnicity of the patients or to the inflammatory state associated with pre-ex isting sickle cell disease.