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动态微小残留病监测对青少年和成人T淋巴细胞白血病/淋巴瘤的预后价值

Prognostic value of dynamic minimal residual disease monitoring for adolescent and adult T-lymphoblastic leukemia/lymphoma.

作者信息

Yang Ying, Zhang Xin, Jiang Nenggang, Jin Yongmei, Liu Yu, Liao Hongyan

机构信息

Department of Laboratory Medicine, Clinical Laboratory Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, China.

Sichuan Clinical Research Center for Laboratory Medicine, Chengdu, 610041, China.

出版信息

Ann Hematol. 2025 Aug 26. doi: 10.1007/s00277-025-06535-3.

DOI:10.1007/s00277-025-06535-3
PMID:40856820
Abstract

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a high-risk malignancy with poor outcomes due to frequent relapse. The prognostic role of minimal residual disease (MRD) dynamic monitoring in adult T-ALL/LBL needs further validation across chemotherapy and transplantation phases. This large-scale study aimed to assess multi-timepoint MRD as a predictive biomarker, and integrated risk factors in adult T-ALL/LBL. 348 T-ALL/LBL patients treated with induction/consolidation chemotherapy ± allogeneic hematopoietic stem cell transplantation (allo-HSCT) were involved. MRD was assessed via multiparameter flow cytometry (MFC) at four landmark timepoints: post-induction (EOI-MRD), post-consolidation (EOC-MRD), pre-HSCT (pre-MRD), and post-HSCT (post-MRD). The prognostic value of routine clinical and laboratory variables was analyzed. The cohort exhibited 10-year OS and EFS rates of 35.0% and 28.2%, respectively. Adverse prognostic factors included thrombocytopenia (PLT ≤ 90 × 10⁹/L; p = 0.0195), elevated LDH (> 600 IU/L; p = 0.0338), cerebrospinal fluid (CSF) infiltration (p = 0.0012), and induction failure (p = 0.0237). HSCT improved outcomes (median OS: 24 vs. 17 months; p = 0.0007), especially in relapsed/refractory (R/R) patients (5-year OS: 40% vs. < 20%; p = 0.0042). MRD positivity predicted inferior survival at all timepoints (EOI-MRD: p = 0.0255; pre-HSCT: p = 0.0156; post-HSCT: p < 0.0001, 100% relapse if positive). Chemotherapy-only patients with sustained MRD negativity had a reduced relapse rate (p = 0.0090) and superior OS (p = 0.0001). In conclusion, dynamic MRD monitoring (pre-/post-HSCT and during chemotherapy) is prognostic in adult T-ALL/LBL. Combined with variables including LDH and MRD kinetics enables precision prognostication and guides therapeutic decision-making, including early HSCT for persistent MRD-positive cases.

摘要

T细胞急性淋巴细胞白血病/淋巴瘤(T-ALL/LBL)是一种高危恶性肿瘤,由于频繁复发,预后较差。微小残留病(MRD)动态监测在成人T-ALL/LBL中的预后作用需要在化疗和移植阶段进行进一步验证。这项大规模研究旨在评估多时间点MRD作为预测生物标志物以及成人T-ALL/LBL中的综合危险因素。研究纳入了348例接受诱导/巩固化疗±异基因造血干细胞移植(allo-HSCT)治疗的T-ALL/LBL患者。通过多参数流式细胞术(MFC)在四个关键时间点评估MRD:诱导后(EOI-MRD)、巩固后(EOC-MRD)、HSCT前(pre-MRD)和HSCT后(post-MRD)。分析了常规临床和实验室变量的预后价值。该队列的10年总生存率(OS)和无事件生存率(EFS)分别为35.0%和28.2%。不良预后因素包括血小板减少(PLT≤90×10⁹/L;p = 0.0195)、乳酸脱氢酶升高(>600 IU/L;p = 0.0338)、脑脊液(CSF)浸润(p = 0.0012)和诱导失败(p = 0.0237)。HSCT改善了预后(中位OS:24个月对17个月;p = 0.0007),尤其是在复发/难治性(R/R)患者中(5年OS:40%对<20%;p = 0.0042)。MRD阳性在所有时间点均预示生存较差(EOI-MRD:p = 0.0255;HSCT前:p = 0.0156;HSCT后:p<0.0001,若阳性则100%复发)。仅接受化疗且MRD持续阴性的患者复发率降低(p = 0.0090),OS更佳(p = 0.0001)。总之,动态MRD监测(HSCT前后及化疗期间)对成人T-ALL/LBL具有预后意义。结合乳酸脱氢酶和MRD动力学等变量能够实现精准预后评估并指导治疗决策,包括对持续MRD阳性病例尽早进行HSCT。

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