Horwitz Mitchell E, Spasojevic Ivan, Morris Ashley, Telen Marilyn, Essell James, Gasparetto Cristina, Sullivan Keith, Long Gwynn, Chute John, Chao Nelson, Rizzieri David
Adult Stem Cell Transplant Program, Division of Cellular Therapy, Duke University School of Medicine, Durham, North Carolina 27710, USA.
Biol Blood Marrow Transplant. 2007 Dec;13(12):1422-6. doi: 10.1016/j.bbmt.2007.08.050.
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.
终末器官损伤在镰状细胞病（SCD）患者中很常见，因此限制了异基因干细胞移植（SCT）的应用。我们报告了2例成年SCD患者的治疗结果，其中1例患有终末期肾病（ESRD），他们接受了来自 HLA 配型相同的同胞供者的基于氟达拉滨的非清髓性SCT。为预防氟达拉滨毒性，患有ESRD的患者在调整氟达拉滨剂量后接受了积极的透析治疗。对患有ESRD的患者以及另外2例肾功能正常的患者研究了氟达拉滨代谢产物F - Ara - A的药代动力学。2例SCD患者均实现了完全供体红细胞嵌合，血细胞计数正常，且未服用免疫抑制药物。通过将剂量降低20%并随后进行每日透析，我们实现了与肾功能正常患者几乎相同的氟达拉滨药物暴露。我们得出结论，对于成年SCD患者，基于氟达拉滨的非清髓性异基因SCT是可行的，即使在ESRD的情况下也是如此。
