Fludarabine-based nonmyeloablative stem cell transplantation for sickle cell disease with and without renal failure: clinical outcome and pharmacokinetics.
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.
Horwitz
Mitchell E
ME
Adult Stem Cell Transplant Program, Division of Cellular Therapy, Duke University School of Medicine, Durham, North Carolina 27710, USA. Mitchell.horwitz@duke.edu
Spasojevic
Ivan
I
Morris
Ashley
A
Telen
Marilyn
M
Essell
James
J
Gasparetto
Cristina
C
Sullivan
Keith
K
Long
Gwynn
G
Chute
John
J
Chao
Nelson
N
Rizzieri
David
D
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
D019653:Myeloablative Agonists; D014740:Vidarabine; C024352:fludarabine