title: Fludarabine-based conditioning for allogeneic transplantation in adults with sickle cell disease.
abstract: Although allogeneic transplantation can be curative for patients with sickle cell disease, the toxicity of conditioning regimens has precluded its use in adults with significant end-organ damage. Newer conditioning regimens have been developed that are less toxic and that may broaden the applicability of allogeneic transplantation in this disorder. We report two adults with end-stage sickle cell disease, who underwent allogeneic transplantation from an HLA-identical sibling donor after conditioning with fludarabine/melphalan and ATG. Both patients had been extensively transfused and one had multiple RBC antibodies. One of the patients also had end-stage renal disease, and was dialysis dependent. Engraftment occurred promptly in both patients. Both achieved 100% donor chimerism and both were free of pain crises after transplant. The first patient died of a respiratory failure related to chronic graft-versus-host disease (GVHD) on day 335 after transplantation. The second patient developed severe gastro-intestinal GVHD and TTP and died on day 147 after transplantation. Conditioning with fludarabine/melphalan and 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 ethnicity of the patients or to the inflammatory state associated with pre-existing sickle cell disease.
authors.affiliation: Section of Hematology/Oncology University of Illinois College of Medicine, Chicago 60612, USA.
authors.forename: K
authors.initials: K
authors.lastname: van Besien
authors.forename: A
authors.initials: A
authors.lastname: Bartholomew
authors.forename: W
authors.initials: W
authors.lastname: Stock
authors.forename: D
authors.initials: D
authors.lastname: Peace
authors.forename: S
authors.initials: S
authors.lastname: Devine
authors.forename: D
authors.initials: D
authors.lastname: Sher
authors.forename: J
authors.initials: J
authors.lastname: Sosman
authors.forename: Y H
authors.initials: YH
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Koshy
authors.forename: R
authors.initials: R
authors.lastname: Hoffman
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000628:therapy*; D017809:Fatal Outcome; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000633:toxicity; D008875:Middle Aged; D009679:Nuclear Family; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods / Q000592:standards; D014184:Transplantation, Homologous / Q000379:methods; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D007166:Immunosuppressive Agents; D014740:Vidarabine; C024352:fludarabine