Minimal residual disease monitoring and preemptive immunotherapies for frequent 11q23 rearranged acute leukemia after allogeneic hematopoietic stem cell transplantation
Minimal residual disease monitoring and preemptive immunotherapies for frequent 11q23 rearranged acute leukemia after allogeneic hematopoietic stem cell transplantation
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异基因造血干细胞移植后频繁发生11q23重排急性白血病的微小残留病监测和先发性免疫治疗
DOI：
10.1007/s00277-021-04488-x
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发表时间：
2021-03-13
影响因子：
3.5
通讯作者：
Mo, Xiao-Dong
中科院分区：
文献类型：
--
作者：
Liu, Jing;Zhang, Xiao-Hui;Mo, Xiao-Dong
11q23/ kmt2a -重排（KMT2A-r）急性白血病（AL）在同种异体造血干细胞移植（alloo - hsct）后预后较差。微小残留病（MRD）是复发的重要预后因素。因此，我们旨在确定接受同种异体造血干细胞移植的患者在接受同种异体造血干细胞移植之前和之后kmt2的演变，以及先发制人的免疫疗法对mt2a -r AL患者的疗效。通过基于taqman的RQ-PCR技术检测kmt2a的表达。预防性免疫治疗包括干扰素-α和供体淋巴细胞输注。我们从177例连续的kmt2a -r AL患者中收集了1751份骨髓样本。pre - hsctkmt2阳性与post- hsctkmt2阳性相关（相关系数=0.371，P<0.001）。同种异体造血干细胞移植前低水平组（>,<0.1%）、中等水平组（≥0.1%,<1%）和高水平组（≥1%）的kmt2阴性率分别为96.6%、92.9%和68.8%。同种异体造血干细胞移植后kmt2阳性恢复率在hsct前kmt2a阴性、低水平、中水平和高水平组分别为7.7%、35.7%、38.5%和45.5% （P<0.001）。与kmt2a阴性组（15.1%）和kmt2a <0.1%组（31.2%）相比，hsctkmt2a前表达≥0.1%组的4年累积复发发生率高达53.7%。hsctkmt2阳性后患者的临床结果较持续kmt2阴性患者差。虽然hsct后先发制人的免疫治疗可能有助于实现ekmt2阴性，但长期疗效并不令人满意。因此，hsctkmt2阳性前与hsctkmt2阳性后显著相关。hsctkmt2阳性后患者的临床预后较差，这可能无法通过常用的免疫疗法来克服。
The prognosis of11q23/KMT2A-rearranged (KMT2A-r) acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poor. Minimal residual disease (MRD) is an important prognostic factor for relapse. Thus, we aimed to identify the evolution ofKMT2Abefore and after allo-HSCT and the efficacy of preemptive immunotherapies forKMT2A-r AL patients receiving allo-HSCT.KMT2Aexpression was determined through TaqMan-based RQ-PCR technology. Preemptive immunotherapies included interferon-α and donor lymphocyte infusion. We collected 1751 bone marrow samples from 177 consecutiveKMT2A-r AL patients. Pre-HSCTKMT2Apositivity was correlated with post-HSCTKMT2Apositivity (correlation coefficient=0.371,P<0.001). The rates of achievingKMT2Anegativity after allo-HSCT were 96.6%, 92.9%, and 68.8% in the pre-HSCT low-level group (>0, <0.1%), intermediate-level group (≥ 0.1%, <1%), and high-level group (≥1%), respectively. The rates of regainingKMT2Apositivity after allo-HSCT were 7.7%, 35.7%, 38.5%, and 45.5% for the pre-HSCTKMT2A-negative, low-level, intermediate-level, and high-level groups, respectively (P<0.001). The 4-year cumulative incidence of relapse after allo-HSCT was as high as 53.7% in the pre-HSCTKMT2Aexpression ≥ 0.1% group, which was compared to theKMT2A-negative group (15.1%) andKMT2A<0.1% group (31.2%). The clinical outcomes of patients with post-HSCTKMT2Apositivity were poorer than those of patients with persistentKMT2Anegativity. Although post-HSCT preemptive immunotherapies might help to achieveKMT2Anegativity, the long-term efficacy was unsatisfactory. Thus, pre-HSCTKMT2Apositivity was significantly associated with post-HSCTKMT2Apositivity. The clinical outcomes of patients with post-HSCTKMT2Apositivity were poor, which might not be overcome by commonly used immunotherapies.