非血缘异基因造血干细胞移植治疗高危难治急性髓系白血病的疗效分析

本研究探讨非血缘异基因造血干细胞移植（URD-HSCT）治疗高危急性髓系白血病（AML）的疗效。22例接受URD-HSCT的高危难治性AML患者纳入研究,采用改良马利兰＋环磷酰胺（20例）或全身放疗＋环磷酰胺（2例）的清髓性预处理方案行URD-HSCT,术后采用环孢素A（CsA）＋甲氨蝶呤（MTX）＋骁悉（MMF）＋ATG预防急性移植物抗宿主病（aGVHD）。结果表明：22例患者中21例（95.5%）获得植入,中性粒细胞和血小板植活的中位时间分别是12（10-19）d和14（5-22）d;中位随访时间18（3-135.5）月,2年的总体生存率（OS）和无白血病生存率（LFS）分别为（53.9±12.2）%和（49.1±10.7）%;移植后8例患者发生aGVHD,累积发生率为（39.1±10.6）%,其中6例为I-II度aGVHD,2例为III-IV度aGVHD;在19例可评估的患者中,慢性GVHD（cGVHD）6例（4例为局限型,2例广泛型）,累积发生率为（28.8±9.6）%;复发7例,2年的累积复发率为（35.8±11）%;死亡原因分析显示,9例死亡中1例死于败血症,1例死于肺部感染,6例死于复发,另外1例复发予化疗联合供体淋巴细胞输注（DLI）治疗缓解后发生IV度aGVHD而死亡;预后因素分析显示,复发是影响生存的主要因素（P〈0.001）,而性别、年龄、移植方式、aGVHD、感染等对生存无明显影响,cGVHD患者生存率高于未发生者（83.3%vs 37%,P=0.152）。结论：单中心样本研究结果显示,URD-HSCT是治疗无合适血缘供体高危AML患者的有效手段,cGVHD患者预后较好,复发是影响患者生存的主要因素,移植后通过过继免疫治疗如DLI可以预防复发并改善预后以获得长期生存。

Efficacy Analysis of Unrelated Donor Hematopoietic Stem Cell Transplantation for Treatment of High Risk Acute Myeloid Leukemia

This study was purposed to investigate the therapeutic efficacy of unrelated donor hematopoietic stem cell transplantation （URD-HSCT） for patients with high risk and refractory acute myeloid leukemia （AML）. Twenty-two patients with high-risk and refractory AML receive URD-HSCT were enrolled in this study. All the patients received myeloablatic preconditioning regimen cosisting of busulfan/cyclophosphamide （ for 20 cases） or total body irradiation/cy- clophosphamide（ for 2 cases） before URD-HSCT. The cyclosporin A（ CsA）/MTX/MMF/ATG were used to prevent the acute graft versus host disease（aGVHD）. The results showed that 21 out of 22 patients acquired engrafment with implantation rate 95.5%. The median time of ANC〉0.5 x 109/L was 12（ 10 - 19） days, and that of Plt〉20 x 109/L was 14 （5 -22） days. The median follow-up time post transplantation was 18（3 to 135.5） months. The 2-year overall survival （OS） and leukemia-free survival （LFS） were （53.9±12.2） % and （49.1 ±10.7 ） % respectively. Eight cases devel- oped aGVHD. The cumulative incidence of aGVHD was （39. 1 ± 10.6 ） %. Six patients developed I - II grade of aGVHD and two patients developed HI -IV grade of aGVHD. The chronic graft versus host disease（cGVHD） was oc-curred in 6 patients （4 patients limited, 2 patients extensive） of the 19 evaluable patients. The cumulative incidence was （28.8 ± 9.6） %. Seven cases relapsed, and the cumulative response rate of 2 years was （35.8 ± 11 ） %. One of 9 pa- tients died from sepsis before hematopoietic reconstruction, one died from lung infection, Six died from relapse and one relapsed patient died from IV grade of aGVHD post chemotherapy and donor lymphocyte infusion（DLI）. The univariate analysis revealed that relapse was the major factor for the OS, and the sex, age, preconditioning regimen, aGVHD and infection didn＇t significantly influence the efficacy of URD-HSCT. The survival of patients with cGVHD was superior to those who didn＇t have cGVHD （83.3 % vs 37%, P = 0. 152 ）. It is concluded that URD-HSCT is a safe and effective therapy for high-risk AML patients without related donor. Notably, patients with cGVHD had a better survival. Relapse is an unfavourable factor for the efficacy of URD-HSCT and adoptive immunotherapy such as DLI can prevent it and improve the prognosis to achieve the long-time survival.