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细胞遗传学和分子诊断特征结合流式细胞术检测巩固后微小残留病评估可改善成人急性髓细胞白血病的危险分层。

Cytogenetic and molecular diagnostic characterization combined to postconsolidation minimal residual disease assessment by flow cytometry improves risk stratification in adult acute myeloid leukemia.

机构信息

Hematology, Fondazione Policlinico Tor Vergata, Viale Oxford 81, Rome, Italy.

出版信息

Blood. 2010 Sep 30;116(13):2295-303. doi: 10.1182/blood-2009-12-258178. Epub 2010 Jun 14.

Abstract

A total of 143 adult acute myeloid leukemia (AML) patients with available karyotype (K) and FLT3 gene mutational status were assessed for minimal residual disease (MRD) by flow cytometry. Twenty-two (16%) patients had favorable, 115 (80%) intermediate, and 6 (4%) poor risk K; 19 of 129 (15%) carried FLT3-ITD mutation. Considering postconsolidation MRD status, patients with good/intermediate-risk K who were MRD(-) had 4-year relapse-free survival (RFS) of 70% and 63%, and overall survival (OS) of 84% and 67%, respectively. Patients with good- and intermediate-risk K who were MRD(+) had 4-year RFS of 15% and 17%, and OS of 38% and 23%, respectively (P < .001 for all comparisons). FLT3 wild-type patients achieving an MRD(-) status, had a better outcome than those who remained MRD(+) (4-year RFS, 54% vs 17% P < .001; OS, 60% vs 23%, P = .002). Such an approach redefined cytogenetic/genetic categories in 2 groups: (1) low-risk, including good/intermediate K-MRD(-) with 4-year RFS and OS of 58% and 73%, respectively; and (2) high risk, including poor-risk K, FLT3-ITD mutated cases, good/intermediate K-MRD(+) categories, with RFS and OS of 22% and 17%, respectively (P < .001 for all comparisons). In AML, the integrated evaluation of baseline prognosticators and MRD improves risk-assessment and optimizes postremission therapy.

摘要

共有 143 例成人急性髓系白血病(AML)患者的核型(K)和 FLT3 基因突变状态可供评估微小残留病(MRD),采用流式细胞术进行检测。22 例(16%)患者 K 为低危,115 例(80%)为中危,6 例(4%)为高危;129 例中有 19 例携带 FLT3-ITD 突变。考虑巩固治疗后 MRD 状态,中危和高危 K 且 MRD(-)的患者 4 年无复发生存率(RFS)分别为 70%和 63%,总生存率(OS)分别为 84%和 67%。中危和高危 K 且 MRD(+)的患者 4 年 RFS 分别为 15%和 17%,OS 分别为 38%和 23%(所有比较均 P <.001)。达到 MRD(-)状态的 FLT3 野生型患者比仍为 MRD(+)的患者预后更好(4 年 RFS,54% vs 17%,P <.001;OS,60% vs 23%,P =.002)。这种方法重新定义了 2 个组的细胞遗传学/遗传学类别:(1)低危,包括中危和高危 K-MRD(-),4 年 RFS 和 OS 分别为 58%和 73%;(2)高危,包括高危 K、FLT3-ITD 突变病例、中危和高危 K-MRD(+),4 年 RFS 和 OS 分别为 22%和 17%(所有比较均 P <.001)。在 AML 中,基线预后因素和 MRD 的综合评估可改善风险评估并优化缓解后治疗。

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