含氟达拉滨的清髓性预处理造血干细胞移植对高危白血病疗效的初步观察

A Preliminary Study on Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation by Myeloablative Conditioning Regimen with Fludarabine for High Risk Leukemia Patients

本研究探讨含氟达拉滨的清髓性预处理造血干细胞移植对高危的白血病的疗效。用氟达拉滨,马利兰和环磷酰胺组成新的预处理方案的异基因造血干细胞移植治疗25例难治、复发的急性白血病,其中非血缘供者10例,血缘供者15例,供受者HLA配型相合者15例,配型不全相合10例。GVHD防治采用环孢素A+甲氨蝶呤联合方案,非血缘供者移植和HLA不相合移植时加用吗替麦考酚酯和抗胸腺T淋巴细胞球蛋白(ATG)。结果显示,10例非血缘供者移植全部成功植活,植入成功率100%,15例亲缘移植14例植活,1例HLA4/6相合者植入失败死亡,植入成功率93.3%。造血重建时间:外周血中性粒细胞计数大于0.5×109/L的中位时间是13(11-19)天,血小板计数大于20×109/L的时间为14(12-20)天。3例发生Ⅱ-Ⅳ度急性GVHD(12.5%),9例发生慢性GVHD(47.4%)。移植后原发病复发死亡率42.1%,随访6到84个月,3年无病生存47.1%。结论:含氟达拉滨的清髓性预处理方案用于高危白血病的异基因移植是安全、有效的,它减少了移植后GVHD发生率和预处理相关的毒副作用,但是移植后恶性疾病复发较高,需要进一步改进。

The aim of this study was to explore the efficacy of allogeneic hematopoietic stem cell transplantation（allo-HSCT） by myeloablative conditioning regimen with fludarabine for high risk leukemia patients.25 refractory and relapsed leukemia patients underwent allo-HSCT with new conditioning regimen consisted of fludarabine,busulfan and cyclophosphamide.Donors for 15 patients were sibling,but donors for the rest 10 patients were all unrelated.HLA matched and mismatched donors were for 15 and 10 patients respectively.The graft versus host disease（GVHD）prophylaxis included cyclosporine A and methotrexate,while mycophenolate mofetil and rabbit anti-T-lymphocyte globulin（ATG） were used in case of unrelated and HLA mismatched HSCT.The results showed that unrelated donor HSCT in 10 cases was successful（100%）,14 out of 15 patients with donors of sibling or parent also reconstructed their haematopoietic system.One mismatched patient（4/6） died of graft failure.The time from transplantation to ANC0.5 ×109/L and Plt20×109/L were 13（11-19） days and 13（12-20） days after transplantation respectively.The cumulative incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD was 12.5%（3/24） and 47.4%（9/19）,respectively.In a follow-up duration of 6-84 months,12 patients were dead,out of which 8 died of relapse;1 cases died of regimen-associated side effect.3 cases died of serious infection.The other 13 patients remained alive and disease-free survival probability was 48.7%.It is concluded that allo-HSCT by myeloablative conditioning regimen with fludarabine is a safe and effective option for high risk leukemia patients,which reduces aGVHD incidence and regimen-associated side effect,but it should be modified for higher rate of relapse.