造血干细胞移植治疗儿童急性髓系白血病的预后分析

Prognostic analysis of hematopoietic stem cell transplantation for treatment of acute myeloid leukemia in children

摘要

目的 探讨影响造血干细胞移植(HSCT)治疗儿童急性髓系白血病(AML)预后的临床因素。方法 选择2016年1月至2022年1月徐州医科大学附属医院收治并完成HSCT的70例AML患儿为研究对象,统计患儿一般临床特征、移植资料、实验室检查,分析影响其总生存率(OS)、无事件生存率(EFS)相关因素。结果 70例患儿随访中位时间33.8(1.9~106.6)月,3年OS 71.6%,3年EFS 63.8%;男性37例,女性33例,发病中位年龄13(3~18)岁,初诊至移植中位时间6(2~18)月,干细胞植入粒系重建时间13(10~16)d,巨核系重建时间为15(10~30)d;单因素分析结果显示,C-KIT突变阳性、微小残留病(MRD)阳性、CD4⁺/CD8⁺低水平、造血重建期输血次数多、供者年龄大、巨细胞病毒(CMV)感染的患儿3年OS较低,差异有统计学意义(χ²分别为4.771、4.746、4.139、5.238、5.014、3.972,P<0.05);C-KIT突变阳性、MRD阳性、CD4⁺/CD8⁺低水平、输血次数多、供者年龄大的患儿3年EFS较低,差异有统计学意义(χ²分别为4.065、4.002、6.601、6.569、4.426,P<0.05);多因素COX回归分析结果显示,C-KIT突变阳性、输血次数多、供者年龄大均是影响3年OS、3年EFS的独立危险因素,其HR值及95%CI分别为2.322(1.071~3.815)、2.057(1.016~6.307)、1.475(1.019~2.135)、2.037(1.006~3.921)、3.109(1.695~6.212)、1.628(1.003~2.601)。结论 C-KIT突变阳性、供者年龄大、造血重建期输血次数多是影响造血干细胞移植治疗儿童急性髓系白血病预后的独立危险因素。

Abstract

Objective To investigate clinical factors affecting prognosis of hematopoietic stem cell transplantation (HSCT) for treatment of acute myeloid leukemia (AML) in children. Methods 70 pediatric AML patients who underwent and completed HSCT in The Affiliated Hospital of Xuzhou Medical University from January 2016 to January 2022 were selected as study cohort. General clinical characteristics, transplantation data, and laboratory results were statistically analyzed to identify factors affecting overall survival (OS) and event-free survival (EFS). Results The median follow-up time was 33.8 months (ranged from 1.9 months to 106.6 months). The 3-year OS and EFS rates were 71.6% and 63.8%, respectively. Among 70 pediatric AML patients, 37 patients were male and 33 patients were female, with a median age at onset of 13 years (ranged from 3 years to 18 years). The median time from initial diagnosis to HSCT was 6 months (ranged from 2 months to 18 months). The time from hematopoietic stem cell engraftment to granulocyte series reconstitution was 13 days (ranged from 10 days to 16 days), and the time from hematopoietic stem cell engraftment to megakaryocytic reconstitution was 15 days (ranged from 10 days to 30 days). Univariate analysis showed that the 3-year OSs of these patients with positive C-KIT mutation, positive minimal residual disease (MRD), low CD4 ⁺/CD8 ⁺ ratio, frequent blood transfusions during hematopoietic reconstitution, older donor's age, and cytomegalovirus (CMV) infection were lower, the differences were significant (χ ²=4.771, 4.746, 4.139, 5.238, 5.014 and 3.972 respectively, all P<0.05). Similarly, the 3-year EFSs of these patients with positive C-KIT mutation, positive MRD, low CD4 ⁺/CD8 ⁺ ratio, frequent blood transfusion during hematopoietic reconstitution and older donor's age were lower, the differences were significant (χ ²=4.065, 4.002, 6.601, 6.569 and 4.426 respectively, all P<0.05). Multivariate Cox regression analysis showed that positive C-KIT mutation, frequent blood transfusion during hematopoietic reconstitution, and older donor's age were independent risk factors for both 3-year OS and 3-year EFS, and their hazard ratios (HR) [95% confidence intervals (CI)] were 2.322 (1.071-3.815), 2.057 (1.016-6.307) and 1.475 (1.019-2.135) for the 3-year OS, and 2.037 (1.006-3.921), 3.109 (1.695-6.212) and 1.628 (1.003-2.601) for the 3-year EFS, respectively. Conclusion C-KIT mutation positivity, older donor's age and frequent blood transfusion during hematopoietic reconstitution are independent risk factors for prognosis of HSCT in pediatric AML patients.

关键词

儿童 / 急性髓系白血病 / 造血干细胞移植 / 预后因素 / 基因突变

Key words

children / acute myeloid leukemia / hematopoietic stem cell transplantation / prognostic factor / gene mutation

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