移植前免疫表型缓解与血液形态学缓解对急性髓系白血病患者同胞HLA相合造血干细胞移植疗效预测价值的比较

Abstract

目的 比较移植前免疫表型缓解(ICR)和血液形态学缓解对急性髓系白血病(AML)患者同胞HLA相合造血干细胞移植(MSDT)疗效的预测价值.方法 回顾性分析182例接受MSDT的AML患者(除外急性早幼粒细胞白血病),将移植前血液形态学缓解分为血细胞恢复的完全缓解(CR)、血小板未恢复的CR(CRp)、血小板和中性粒细胞均未恢复的CR(CRi),将多参数流式细胞术检测微小残留病阴性定义为ICR.结果 ①全部182例AML患者中,男97例,女85例,中位年龄41(4～62)岁.②移植前CR、CRp+CRi率分别为80.8％(147/182)、19.2％(35/182);移植前CRp+CRi组、CR组的预期4年累积复发率(CIR)[(11.044.3)％对(16.0士7±1)％,x2=0.274,P=0.600]、非复发死亡率(NRM)[(14.0士4±3)％对(9.0士6±3)％,x2=0.913,P=0.339]、无白血病生存(LFS)率[(75.0±5.1)％对(75.0±8.3)％,x2=0.256,P=0.613]、总生存(OS)率[(77.0±5.2)％对(80.0±8.1)％,x2=0.140,P=0.708]差异均无统计学意义.③移植前ICR组(147例)与非ICR组(35例)比较,4年CIR较低[(11.3士3.4)±对(55.2±8.8)％,x2=32.687,P＜ 0.001],LFS率[(76.2±4.7)％对(32.8士8.7)％,x2=26.234,P＜0.001]和OS率[(79.0±4.7)％对(39.0士9.1)％,x2±25.253,P＜0.001]较高,NRM差异无统计学意义[(12.5士4.1)％对(12.0±7.1)％,x2=1.002,P=0.656].④多因素分析显示,移植前非ICR是影响AML患者MSDT后复发[HR=11.026 (95％ CI 4.685～ 25.949),P＜0.001]、LFS [HR=5.785 (95％ CI 2.974～ 11.254),P＜0.001]和OS [HR=5.578 (95％CI 2.575～ 27.565),P＜ 0.001]的独立危险因素.结论 移植前ICR对AML患者MSDT的疗效预测价值优于HCR.

Objective To assess the prognostic significance of immunophenotype complete remission (ICR) and hematological complete remission (HCR) before human-leukocyte antigen (HLA)-matched sibling donor transplantation (MSDT) in acute myeloid leukemia (AML) patients.Methods A cohort of 182 AML (non-APL) patients undergoing MSDT in HCR was retrospectively studied [including complete remission with ANC and PLT recovery (CR),CR with incomplete PLT recovery (CRp),CR with inconplete ANC and PLT recovery (CRi)];ICR was determined as undetective minimal resudial disease (MRD) by multi-parameter flow cytometer.Results ①Ofthe 182 patients,97 were male,85 female,and the median age was 41(4-62) years.②The CR and CRi+CRp rates were 80.8％ (147/182) and 19.2％(35/182),respectively;The 4-year cumulative incidence of relapse [CIR,(11.0 ± 4.3)％ vs (16.0 ± 7.1)％,x2 =0.274,P =0.600],non-relapse mortality [NRM,(14.0 ± 4.3)％ vs (9.0 ± 6.3)％,x2 =0.913,P=0.339],leukemia-free survival [LFS,(75.0±5.1)％ vs (75.0±8.3)％,x2 =0.256,P =0.613],and overall survial [OS,(77.0 ± 5.2)％ vs (80.0 ± 8.1)％,x2 =0.140,P =0.708] were comparable between the CRp+ CRi and CR groups.③Compared with the non-ICR group (n =35),the ICR group (n =147) showed lower 4-year CIR [(11.3±3.4).％ vs (55.2±8.8) ％,x2 =32.687,P＜ 0.001],better 4-year LFS [(76.2±4.7)％ vs (32.8±8.7)％,x2 =26.234,P ＜ 0.001] and OS [(79.0 ± 4.7)％ vs (39.0 ± 9.1)％,x2 =25.253,P ＜ 0.001],and comparable NRM [(12.5 ± 4.1)％ vs (12.0 ± 7.1)％,x2=1.002,P=0.656].④ Mulitvariate analysis confirmed the independent prognostic value of ICR in lower CIR [HR =11.026(95％CI 4.685-25.949),P ＜ 0.001],higher LFS [HR =5.785 (95％ CI 2.974-11.254),P ＜ 0.001] and OS [HR =5.578 (95％ CI 2.575-27.565),P ＜0.001].Conclusion The results indicated that ICR instead of HCR pre-transplantation had a significant prognostic value in AML patients undergoing MSDT.