异基因造血干细胞移植治疗难治／复发急性髓系白血病的疗效及预后因素分析

Allogeneic hematopoietic stem cell transplantation for treatment of refractory and relapsed acute myeloid leukemia： outcomes and prognostic factors

目的评价异基因造血干细胞移植（allo-HSCT）治疗难治／复发急性髓系白血病（AML）的疗效，并对预后相关因素进行分析。方法回顾性分析allo．HSCT治疗99例难治／复发AML患者总体生存（os）率、无病生存（DFS）率、移植物抗宿主病（GVHD）发生率、移植相关死亡率（TRM）及复发率，并分析影响预后的危险因素。结果全部99例患者中男59例，女40例，中位年龄为35（6～58）岁，均接受清髓性预处理。所有患者中性粒细胞均达植入标准，中位植活时间为14（9～25）d。移植后100dⅡ～Ⅳ度急性GVHD累积发生率为27．3％（95％CI18．9％～36．3％）；2年慢性GVHD累积发生率为33．9％（95％CI24．6％～43．5％），其中广泛型慢性GVHD累积发生率为9_3％（95％CI4．5％-16．1％）。移植后3年OS、DFS、TRM率分别为45．0％（95％CI34．6％～55．4％）、45．0％（95％CI34．8％～55．2％）、19．7％（95％a12．4％～28．3％），复发率为36．6％（95％C126．9％～46．4％）。多因素分析显示．影响OS的独立危险因素包括移植前未缓解[P：0．009，HR=2．21（95％CI1．22～4．04）]、初诊WBC〉50×10^9／L[P=0．024，HR=2．11（95％CI1．11～4．02）]、供者年龄〉35岁[P=0．031，HR=1．96（95％CI1．06～3．60）]、移植后未发生慢性GVHD[P=0．008，HR：0．38（95％CI0．18—0．78）]。根据移植前危险因素（移植前未缓解、初诊WBC〉50x107L、供者年龄〉35岁）进行危险度分组，具有0、1、2～3个危险因素患者的3年OS率分别为75．0％、46．9％、15．4％（x^2=26．873，P〈0．001）。结论allo-HSCT是挽救性治疗难治／复发AML的有效手段，复发是影响生存的主要原因。移植前缓解状态、发病时WBC水平、供者年龄及移植后是否发生慢性GVHD是难治／复发AML患者allo—HSCT预后的独立影响因素。

Objective To evaluate the outcomes and prognostic factors of patients with refractory and relapsed acute myeloid leukemia （AML） who received allogeneic hematopoietic stem cell transplantation （allo-HSCT）. Methods The overall survival （OS）, disease free survival （DFS）, acute and chronic graft-versus-host disease （GVHD）, relapse rate （RR）, transplantation related mortality （TRM） and their related risk factors were analyzed retrospectively. Results All the patients （median age 35 years, range 6 to 58） received myeloablative conditioning regimens. All patients had successful engraftment, and the median time of neutrophils engraftment was 14 days （range 9 to 25）. Of the patients who survived more than 100 days, the accumulative incidence of grade II- IV acute GVttD and chronic GVHD （cGVHD） were 27.3% （95% CI 18.9%-36.3% ）, 33.9% （95% CI 24.6%-43.5% ）, respectively. Meanwhile, the accumulative incidence of extensive cGVHD was 9.3% （95%CI 4.5%-16.1% ）. The 3-year OS, DFS, RR, and TRM was 45.0% （95%CI 34.6%-55.4%）, 45.0%（95%CI 34.8%-55.2%）, 36.6%（95% C1 26.9%- 46.4% ） and 19.7% （95% CI 12.4%- 28.3% ） respectively. Multivariate analysis revealed four independent risk factors： non remission status before transplantation [P= 0.009, HR = 2.21 （95%CI 1.22- 4.04） ], WBC at diagnosis 〉 50×10^9/L [P= 0.024, HR = 2.11 （95%CI 1.11-4.02） ], donor age 〉 35 years [P = 0.031, HR = 1.96 （95% CI 1.06- 3.60） ] and without cGVHD [P = 0.008, HR = 0.38 （95% CI 0.18- 0.78） ]. According to the risk factors before transplantation （non remission status, WBC at diagnosis 〉 50×10^9/L, donor age 〉 35 years）, we then defined three subgroups with striking different OS at 3 years： no adverse factor （75.0%）; one adverse factor （46.9%）; two or three adverse factors （15.4%） （x^2 = 26.873, P〈0.001）. Conclusion Allo-HSCT is a promising and safe choice for patients with refractory and relapsed AML and relapse is the major cause of the transplantation failure. Disease status before transplantation, donor age, WBC at diagnosis and cGVHD are confirmed as prognostic factors for these patients who received allo-HSCT.