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早期(诊断后第 15 天)外周血流细胞术检测微小残留病是儿童 B 细胞淋巴母细胞白血病预后的强有力预测指标。

Early (Day 15 Post Diagnosis) Peripheral Blood Assessment of Measurable Residual Disease in Flow Cytometry is a Strong Predictor of Outcome in Childhood B-Lineage Lymphoblastic Leukemia.

机构信息

APHM, Laboratoire d'Hématologie, Hôpital La Timone, Marseille, France.

CNRS, INSERM, CIML, Aix Marseille University, Marseille, France.

出版信息

Cytometry B Clin Cytom. 2019 Mar;96(2):128-133. doi: 10.1002/cyto.b.21769. Epub 2019 Feb 7.

Abstract

BACKGROUND

In children with acute lymphoblastic leukemia (ALL) low levels of minimal residual disease (MRD) after induction, essentially assessed in the bone marrow, have been shown to be of good prognosis. However, only few studies have tested the peripheral blood for MRD.

METHODS

Here, we report the impact on survival of peripheral blood (PB) MRD assessment by multiparameter flow cytometry (MFC) at early time points of treatment in 125 B-ALL children, compared to Day 35 molecular bone marrow (BM) MRD. Patients were sampled for MFC one week postdiagnosis after a pre-phase of corticotherapy (Day 8), then after one week of chemotherapy (Day 15). The study enrolled 67 boys and 58 girls with a median follow-up of 52 months. Over the duration of the study, 20 patients relapsed and eight died. MFC was performed based on the leukemia-associated immunophenotype at diagnosis, using panels of 10 antibodies.

RESULTS

Although, PB MFC-MRD had no prognostic impact at Day 8, Day 15 MRD negativity was associated with a significantly better 4 years DFS (91.6 ± 3% vs. 67.6 ± 9% P = 0.0013). Furthermore, while MFC and molecular data were concordant in most cases, patients with detectable PB MRD on Day 15, yet negative in BM on Day 35 had a significantly lower DFS (P < 0.0001).

CONCLUSION

This study demonstrates that the less invasive procedure of MFC-MRD assessment in PB can be informative for childhood ALL patients at the early point of Day 15 of the treatment schedule. © 2019 International Clinical Cytometry Society.

摘要

背景

在诱导后骨髓中检测到低水平微小残留病(MRD)的急性淋巴细胞白血病(ALL)患儿具有良好的预后。然而,仅有少数研究检测了外周血中的 MRD。

方法

我们报道了在 125 例 B-ALL 患儿中,治疗早期通过多参数流式细胞术(MFC)检测外周血(PB)MRD 对生存的影响,并与第 35 天骨髓(BM)MRD 进行比较。患者在皮质激素治疗前阶段(第 8 天)后一周和化疗后一周(第 15 天)进行 MFC 取样。研究纳入了 67 名男性和 58 名女性患儿,中位随访时间为 52 个月。在研究期间,有 20 名患者复发,8 名患者死亡。MFC 基于诊断时的白血病相关免疫表型进行,使用 10 种抗体的组合进行检测。

结果

尽管第 8 天的 PB-MFC-MRD 无预后意义,但第 15 天的 MRD 阴性与显著更好的 4 年无病生存率(DFS)相关(91.6 ± 3%比 67.6 ± 9%,P = 0.0013)。此外,虽然 MFC 和分子数据在大多数情况下是一致的,但在第 15 天 PB 中可检测到 MRD 而在第 35 天 BM 中阴性的患者,DFS 显著较低(P < 0.0001)。

结论

本研究表明,在治疗计划的第 15 天早期,通过 PB 进行侵袭性较小的 MFC-MRD 评估可为儿童 ALL 患者提供信息。© 2019 国际临床细胞化学协会。

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