异基因造血干细胞移植治疗染色体核型预后中等急性髓系白血病

Allogeneic hematopoietic stem cell transplantation for intermediate cytogenetic risk acute myeloid leukemia

背景:以往研究显示完全缓解期染色体核型预后中等的急性髓系白血病患者行亲缘全相合异基因外周血造血干细胞移植有较高的无病生存率和总体生存率,但影响移植预后的相关因素并未完全明确。目的:评价HLA相合异基因外周血造血干细胞移植治疗完全缓解期染色体核型预后中等急性髓系白血病的疗效,并对预后相关因素进行分析。方法:对2009年1月至2015年1月进行HLA全相合异基因外周血造血干细胞移植的50例完全缓解期染色体核型预后中等的急性髓系白血病患者进行回顾性分析,计算总体生存率,并对影响预后的各因素进行统计学分析。结果与结论:(1)4年总体生存率为64%,累积复发率及移植相关非复发死亡率分别为18%及20%。急性移植物抗宿主病的总体发生率为26%;(2)女性供者男性受者配对移植患者4年总体生存率低于非女性供者男性受者移植患者(P=0.041);移植前大于1个疗程才能达完全缓解的患者4年总体生存率低于移植前1个疗程能达完全缓解的患者(P=0.038);年龄≥40岁的患者4年总体生存率低于年龄<40岁的患者(P=0.056);亲缘供者移植和非亲缘移植患者的4年总体生存率差异无显著性意义(P=0.427)。女性供者男性受者移植及年龄≥40岁患者移植相关非复发死亡率明显增高(P值分别为0.024和0.043);(3)多因素分析确认,与移植预后相关的因素有:女性供者男性受者配对移植(P=0.031,RR=1.38,95%CI 1.03-1.95)、移植前大于1个疗程才能达完全缓解(P=0.016,RR=1.46,95%CI 1.10-1.98)、年龄≥40岁(P=0.024,RR=1.63,95%CI 1.32-2.12);(4)结果表明,HLA全相合异基因外周血造血干细胞移植是染色体核型预后中等急性髓系白血病缓解后治疗的有效方法。女性供者男性受者配对移植、移植前大于1个疗程才能达完全缓解、年龄≥40岁是影响这类患者预后的主要危险因素。这类患者行异基因外周血造血干细胞移植时,供者受者的性别组合比是否为亲缘供者更为重要。

BACKGROUND： Previous studies have shown that HLA-identical sibling allogeneic peripheral blood hematopoietic stem celltransplantation（allo-HSCT） provides higher disease-free and overall survival rates for patients with intermediate cytogenetic risk acute myeloid leukemia（AML） in complete remission（CR）. But prognosis factors have not been fully defined.OBJECTIVE：To evaluate the outcome of patients with intermediate cytogenetic risk AML undergoing HLA-matched allo-HSCT in CR,and to analyze the prognostic factors.METHODS：Fifty cases of intermediate cytogenetic risk AML in CR receiving HLA-matched allo-HSCT from January2009 to January 2015 were retrospectively analyzed.Primary outcome measures of the study included overall survival（OS）,relapse rate and non-relapse mortality.RESULTS AND CONCLUSION：The 4-year OS of the study population reached to 64%,and the relapse rate and NRM reached to 18%and 20%respectively.Incidence of acute graft-versus-host disease was 26%.Different prognosis was observed between female donor/male recipient（FDMR）combination transplant and control（4-year OS：50%vs.71.9%,P=0.041）,between patients requiring more than one course of induction chemotherapy to achieve CR and control（4-year OS：40%vs.70%,P=0.038）,between older age（≥40 years）and control（4-year OS：44.4%vs.68.3%,P=0.056）.The 4-year OS for matched sibling donor and matched unrelated donor was 63.2%and 66.7%（P=0.427）,respectively.Further analysis revealed significantly high non-relapse mortality in FDMR combination transplant（P=0.024）and older age（≥40 years;P=0.043）.Multivariate analysis revealed three negative prognostic factors：FDMR combination（P=0.031,RR=1.38,95%CI：1.03-1.95）,requiring more than one course of induction chemotherapy to achieve CR（P=0.016,RR=1.46,95%CI：1.10-1.98）and older age（≥40 years;P=0.024,RR=1.63,95%CI：1.32-2.12）.To conclude,HLA-matched allo-HSCT is a choice for the intermediate cytogenetic risk AML case in CR.FDMR combination,requiring more than one course of induction chemotherapy to achieve CR and older age（≥40 years）are confirmed as risk factors of poor prognosis for HLA-matched allo-HSCT patients with intermediate cytogenetic risk AML in CR.To these cases,the donor-recipient sex combination is more important than the donor type in donor selection.