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异基因造血干细胞移植治疗急性淋巴细胞白血病的微小残留病评估与干预

Measurable residual disease of acute lymphoblastic leukemia in allograft settings: how to evaluate and intervene.

机构信息

National Clinical Research Center for Hematologic Disease, Peking University People's Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation , Beijing, P.R.C.

出版信息

Expert Rev Anticancer Ther. 2020 Jun;20(6):453-464. doi: 10.1080/14737140.2020.1766973. Epub 2020 May 27.

Abstract

INTRODUCTION

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a curable strategy for acute lymphoblastic leukemia (ALL), especially for adult cases. However, leukemia relapse after allograft restricts the improvement of transplant outcomes. Measurable residual disease (MRD) has been the strongest predictor for relapse after allo-HSCT, allowing MRD-directed preemptive therapy.

AREAS COVERED

This manuscript summarizes the detection of MRD in patients with ALL who undergo allo-HSCT, focusing the effects of positive pre-HSCT MRD and post-HSCT MRD on outcomes as well as MRD-directed interventions.

EXPERT OPINION

Except for MFC and RQ-PCR, other strategies, such as next-generation sequencing and RNAseq, have been developed for MRD determination. Negative effects of positive MRD peri-transplantation on outcomes of ALL patients were observed both in human leukocyte antigen (HLA)-matched sibling donor transplantation and in alternative donor transplantation. Advances have been made in determining the need for transplant according to MRD evaluation after induction or consolidation therapy. A number of approaches, including CAR-T-cell therapy, antibodies (blinatumomab, etc), targeted therapy (imatinib, etc), transplant donor selection, as well as donor lymphocyte infusion and interferon-α, have been successfully used or are promising for peri-transplantation MRD interventions. This progress could lead to the significant improvement of transplant outcomes for ALL patients.

摘要

简介

异基因造血干细胞移植(allo-HSCT)仍然是治疗急性淋巴细胞白血病(ALL)的一种可行策略,尤其适用于成人病例。然而,移植后白血病复发限制了移植结果的改善。微小残留病(MRD)是 allo-HSCT 后复发的最强预测因子,允许进行 MRD 导向的抢先治疗。

涵盖领域

本文总结了接受 allo-HSCT 的 ALL 患者中 MRD 的检测,重点关注移植前阳性 MRD 和移植后 MRD 对结局的影响,以及 MRD 导向的干预措施。

专家意见

除了 MFC 和 RQ-PCR 外,其他策略,如下一代测序和 RNAseq,也已被用于 MRD 检测。在 HLA 匹配的同胞供体移植和替代供体移植中,均观察到移植前阳性 MRD 对 ALL 患者结局的负面影响。在诱导或巩固治疗后根据 MRD 评估确定是否需要移植方面取得了进展。许多方法,包括 CAR-T 细胞疗法、抗体(blinatumomab 等)、靶向治疗(伊马替尼等)、移植供体选择,以及供体淋巴细胞输注和干扰素-α,已被成功应用或在移植前 MRD 干预方面具有前景。这一进展可能导致 ALL 患者移植结果的显著改善。

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