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.

Duke Scholars

Author Mitchell Eric Horwitz Medicine, Hematologic Malignancies and Cellular Therapy

Author Ivan Spasojevic Medicine, Medical Oncology

Author Marilyn Jo Telen Medicine, Hematology

Author Cristina Gasparetto Medicine, Hematologic Malignancies and Cellular Therapy

Author Keith Michael Sullivan Medicine, Hematologic Malignancies and Cellular Therapy

Author Gwynn Douglas Long Medicine, Hematologic Malignancies and Cellular Therapy

Author Nelson Jen An Chao Medicine, Hematologic Malignancies and Cellular Therapy