异基因造血干细胞移植治疗恶性血液病104例临床分析

Clinical analysis of 104 patients with hematological malignancy after allogeneic hemotopoietic stem cell transplantation

目的:评价异基因造血干细胞移植治疗恶性血液病的疗效。方法:对1999年12月至2010年1月间在湘雅医院接受异基因造血干细胞移植(allo-HSCT)的104例恶性血液病患者进行回顾性分析。采用Kaplan-Meier法计算移植后患者移植相关死亡率(TRM)、复发率(RR)、5年总生存率(OS)及5年无病生存率(DFS),并对影响预后的各因素进行统计学分析。结果:101例重建造血。至随访终点,重度急性移植物抗宿主病(aGVHD)的发生率为15.38%,广泛型慢性移植物抗宿主病(cGVHD)发生率为25.53%。TRM及RR分别为15.66%和21.76%,5年OS及DFS分别为(73.49±4.59)%和(63.10±5.32)%,其中急性髓系白血病(AML)患者分别为(63.00±9.51)%和(49.30±9.96)%;慢性粒细胞白血病(CML)患者分别为(83.87±5.06)%和(74.55±6.79)%。生存分析显示女性、重度aGVHD、难治性恶性血液病是预后不良的危险因素,进一步多因素分析显示重度aGVHD、难治性恶性血液病为预后不良的独立危险因素(P<0.05)。重度aGVHD、难治性恶性血液病组患者5年DFS分别为(48.22±12.69)%及(42.09±12.31)%。重度aGVHD、HLA不合、非血缘移植组患者TRM明显高于各自对照组(57.14%vs.4.81%,33.33%vs.10.41%,26.09%vs.9.28%;均P<0.05)。难治性恶性血液病患者RR明显高于其对照组(41.09%vs.15.63%,P<0.05)。结论:allo-HSCT可有效延长恶性血液病患者的无病生存时间,是恶性血液病治疗的重要方法。重度aGVHD、难治性恶性血液病是影响恶性血液病患者allo-HSCT预后的主要危险因素。

Objective To study the efficacy of allogeneic hemotopoietic stem cell transplantation （allo-HSCT） for hematological malignancy. Methods A total of 104 patients with hematological malignancy, who underwent allo-HSCT in Xiangya Hospital from December 1999 to January 2010, were retrospectively analyzed. Of the patients, the transplantation related mortality （TRM）, relapse rate （ RR）, 5-year overall survival （OS） and disease free survival （DFS） were estimated byKaplan-Meier analysis. The unfavorable prognostic factors were also statistically examined. Results Hematopoietic reconstitution was achieved in 101 patients. At the last data of follow-up, the incidences of severe acute graft versus host disease （aGVHD） and extensive chronic GVHD were 15.38% and 25.53% , and the TRM and RR were 15.66% and 21.76% , respectively. The estimated 5-year OS and DFS for all patients were （73.49 ±4.59）% and （63.10 ±5.32）%, respectively. Those for acute myeloid leukemia （AML） patients were （63.00 ±9.51 ）% and （49.30 ± 9.96） %, and those for chronic myeloid leukemia （CML） patients were （83.87± 5.06） % and （74.55 ± 6.79） % , respectively. The survival analysis suggested the poor prognostic factors for allo-HSCT recipients including female sex, severe aGVHD and refractory hematological malignancy. Further multivariate analyses revealed that severe aGVHD and refractory hematological malignancy were the independent risk factors of poor prognosis for the recipients （ P 〈 0.05 ）. The 5-year DFS of severe aGVHD and refractory hematological malignancy patients was （48. 22 ± 12. 69 ）% and （42.09 ± 12.31 ） % , respectively. The TRM of severe aGVHD, HLA-mismatehed graft and unrelated donor transplant was significantly higher than that of the corresponding control groups （57.14% vs. 4.81% , 33.33% vs. 10.41% , 26.09% vs. 9.28% ; P 〈0.05）. The RR of refractory hema- tological malignancy was significantly higher than that of the control group （41.09% vs. 15.63% , P 〈 0.05 ）. Conclusion The treatment of allo-HSCT can improve the disease free survival of pa- tients with hematological malignany and is an important therapeutic method for hematological malignancy. Severe aGVHD and refractory hematological malignancy are the independent risk factors of poor prognosis for the allo-HSCT recipients with hematological malignancy.