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流式细胞术检测微小残留病可对 T 细胞急性淋巴细胞白血病进行可靠的危险分层。

Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia.

机构信息

Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Helsinki University Ctrl. Hospital, Helsinki, Finland.

出版信息

Leukemia. 2019 Jun;33(6):1324-1336. doi: 10.1038/s41375-018-0307-6. Epub 2018 Dec 14.

Abstract

Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4-9.0, p = 0.008) for day 29 FCM-MRD ≥ 10 and 5.6 (95% CI 2.0-16, p = 0.001) for PCR-MRD ≥ 10 compared with MRD < 10. Patients stratified to intermediate-risk therapy on day 29 with MRD 10-<10 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10 had a cumulative incidence of relapse of 2.3% (95% CI 0-6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.

摘要

微小残留病 (MRD) 经克隆性 IgH/TCR 重排的 PCR 测量可预测 T 细胞急性淋巴细胞白血病 (T-ALL) 的复发,并作为风险分层工具。由于 10%的患者没有合适的 PCR 标志物,我们评估了基于流式细胞术 (FCM) 的 MRD 用于风险分层。我们纳入了 274 例接受 NOPHO-ALL2008 方案治疗的 T-ALL 患者。MRD 通过六色 FCM 和实时定量 PCR 测量。第 29 天 PCR-MRD(临界值 10)用于风险分层。在诊断时,93%的患者有用于 MRD 监测的 FCM 标志物,84%的患者有 PCR 标志物,当两种标志物结合时,99.3%(272/274)的患者有标志物。调整年龄和 WBC 后,第 29 天 FCM-MRD≥10 的患者复发风险比为 3.55(95%CI 1.4-9.0,p=0.008),PCR-MRD≥10 的患者复发风险比为 5.6(95%CI 2.0-16,p=0.001),与 MRD<10 的患者相比。第 29 天 MRD 为 10-<10 的患者被分层为中危治疗,与 MRD<10 或无法检测的中危患者相比,5 年无事件生存率相似,无论采用何种监测方法。第 15 天 FCM-MRD<10 的患者累积复发率为 2.3%(95%CI 0-6.8,n=59)。因此,FCM-MRD 可早期识别适合低强度治疗的患者,但这需要进一步研究。总之,FCM-MRD 为 T-ALL 提供可靠的风险预测,并可在没有 PCR 标志物时用于分层。

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