title: Fludarabine-based nonmyeloablative stem cell transplantation for sickle cell disease with and without renal failure: clinical outcome and pharmacokinetics.
abstract: End-organ damage is common in patients with sickle cell disease (SCD) thereby limiting the use of allogeneic stem cell transplantation (SCT). We report the outcome of 2 adult SCD patients, 1 with end-stage renal disease (ESRD), who underwent fludarabine-based nonmyeloablative SCT from HLA-identical matched siblings. To prevent fludarabine toxicity, the patient with ESRD underwent aggressive dialysis following adjusted fludarabine dosing. Pharmacokinetics of the fludarabine metabolite F-Ara-A was studied on the patient with ESRD and 2 additional patients with normal renal function. Both patients with SCD achieved full donor erythroid chimerism, have normal blood counts, and are on no immunosuppressive medications. With a 20% dose reduction followed by daily dialysis, we achieved fludarabine drug exposure that is nearly identical to that achieved in patients with normal renal function. We conclude that fludarabine-based nonmyeloablative allogeneic SCT for adult patients with SCD is feasible, even in the setting of ESRD.
authors.affiliation: Adult Stem Cell Transplant Program, Division of Cellular Therapy, Duke University School of Medicine, Durham, North Carolina 27710, USA. Mitchell.horwitz@duke.edu
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Horwitz
authors.forename: Ivan
authors.initials: I
authors.lastname: Spasojevic
authors.forename: Ashley
authors.initials: A
authors.lastname: Morris
authors.forename: Marilyn
authors.initials: M
authors.lastname: Telen
authors.forename: James
authors.initials: J
authors.lastname: Essell
authors.forename: Cristina
authors.initials: C
authors.lastname: Gasparetto
authors.forename: Keith
authors.initials: K
authors.lastname: Sullivan
authors.forename: Gwynn
authors.initials: G
authors.lastname: Long
authors.forename: John
authors.initials: J
authors.lastname: Chute
authors.forename: Nelson
authors.initials: N
authors.lastname: Chao
authors.forename: David
authors.initials: D
authors.lastname: Rizzieri
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000628:therapy*; D033001:Directed Tissue Donation; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D019653:Myeloablative Agonists / Q000493:pharmacokinetics* / Q000627:therapeutic use; D035781:Siblings; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous / Q000379:methods; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D019653:Myeloablative Agonists; D014740:Vidarabine; C024352:fludarabine