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多参数流式细胞术检测的移植前微小残留病对异基因干细胞移植后FLT3-ITD阳性急性髓系白血病患者预后的影响

Impact of pre-transplantation minimal residual disease determined by multiparameter flow cytometry on the outcome of AML patients with FLT3-ITD after allogeneic stem cell transplantation.

作者信息

Zhao Xiaosu, Wang Zhidong, Ruan Guorui, Liu Yanrong, Wang Yu, Zhang Xiaohui, Xu Lanping, Huang Xiaojun, Chang Yingjun

机构信息

Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Beijing, 100044, China.

Collaborative Innovation Center of Hematology, Peking University, Beijing, China.

出版信息

Ann Hematol. 2018 Jun;97(6):967-975. doi: 10.1007/s00277-018-3265-1. Epub 2018 Feb 8.

Abstract

In this study, using multiparameter flow cytometry (FCM), we investigate the impact of minimal residual disease prior to transplantation (pre-MRD) on the transplant outcomes of AML patients with fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutation. A total of 20 patients who received HLA-matched sibling donor transplantation (MSDT) and 63 patients who received unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT) were enrolled. Patients were classified into four groups based on the status of pre-FCM: group 1 with positive pre-FCM before MSDT, group 2 with negative pre-FCM before MSDT, group 3 with positive pre-FCM before haplo-HSCT, and group 4 with positive pre-FCM before haplo-HSCT. The results showed that patients in group 1 had the highest cumulative incidence of relapse (2-year CIR, 75.0%), the lowest leukemia-free survival (2-year LFS, 33.3%), and the overall survival (2-year OS, 25.0%) among all four groups. The other three groups of patients had comparable CIR (2-year CIR: group 2 vs. 3 vs. 4, 12.5% vs. 31.3% vs. 22.2%, P > 0.05) and LFS (2-year LFS: group 2 vs. 3 vs. 4, 87.5% vs. 62.5% vs. 66.5%, P > 0.05). Multivariate analysis indicated that disease status (> CR) and pre-MRD were associated with a higher CIR and a lower LFS when patients were classified by pre-MRD and transplant type. Our results suggested that AML patients with FLT3-ITD were able to be separated into high-risk and low-risk relapse groups based on pre-MRD, as determined by multiparameter FCM. Haplo-HSCT might overcome the negative impact of pre-MRD on patient outcomes compared to MSDT. These results require further investigation in prospective study with large numbers of cases.

摘要

在本研究中,我们使用多参数流式细胞术(FCM),调查移植前微小残留病(pre-MRD)对伴有FMS样酪氨酸激酶3(FLT3)-内部串联重复(ITD)突变的急性髓系白血病(AML)患者移植结局的影响。共纳入20例接受人类白细胞抗原(HLA)匹配同胞供者移植(MSDT)的患者和63例接受未处理的单倍体相合造血干细胞移植(haplo-HSCT)的患者。根据FCM检测前的状态将患者分为四组:组1为MSDT前FCM检测阳性,组2为MSDT前FCM检测阴性,组3为haplo-HSCT前FCM检测阳性,组4为haplo-HSCT前FCM检测阳性。结果显示,组1患者的复发累积发生率最高(2年累积复发率[CIR],75.0%),无白血病生存率最低(2年无白血病生存率[LFS],33.3%),总生存率(2年总生存率[OS],25.0%)在所有四组中最低。其他三组患者的CIR相当(2年CIR:组2 vs.组3 vs.组4,12.5% vs. 31.3% vs. 22.2%,P>0.05),LFS也相当(2年LFS:组2 vs.组3 vs.组4,87.5% vs. 62.5% vs. 66.5%,P>0.05)。多变量分析表明,当根据pre-MRD和移植类型对患者进行分类时,疾病状态(>完全缓解[CR])和pre-MRD与较高的CIR和较低的LFS相关。我们的结果表明,通过多参数FCM确定,伴有FLT3-ITD的AML患者能够根据pre-MRD分为高风险和低风险复发组。与MSDT相比,haplo-HSCT可能克服pre-MRD对患者结局的负面影响。这些结果需要在大量病例的前瞻性研究中进一步调查。

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