Prognostic Relevance of Treatment Response Measured by Flow Cytometric Residual Disease Detection in Older Patients With Acute Myeloid Leukemia
Prognostic Relevance of Treatment Response Measured by Flow Cytometric Residual Disease Detection in Older Patients With Acute Myeloid Leukemia
复制标题
DOI：
10.1200/jco.2013.49.1753
复制
发表时间：
2013-11-10
影响因子：
45.3
通讯作者：
Burnett, Alan K.
中科院分区：
文献类型：
--
作者：
Freeman, Sylvie D.;Virgo, Paul;Burnett, Alan K.
目的老年急性髓系白血病(AML)患者标准化疗后复发率较高。我们调查了在英国国家癌症研究所AML16试验中，用多参数流式细胞术检测微小残留病(MFC-MRD)检测化疗敏感性是否对60岁以上的患者具有预后价值，或者只是替代已知的年龄相关危险因素。833例患者有白血病相关免疫表型(LAIP)，经预处理筛查确定。427名患者在一个或两个疗程(分别指定为C1和C2)后进入完全缓解(CR)，并至少在这些时间点中的一个时间点通过骨髓LAIP检测评估MFC-MRD。结果MFC-MRD阴性者中有51%(n=286)和(n=279)在C2(n=279)后出现MFC-MRD阴性者，CR后3年存活率显著提高(在MRD阳性患者中分别为42%和26%，P<；.001；C2：38%和18%，P<；.001)，并减少了复发(在MRD阳性患者中，分别为71%和83%，P<；.001；C2：79%和91%；P<；.001；C2：72%和91%；P<；.001；C2：79%vs91%；P<；.001；.001)，MRD阳性患者早期复发的风险较高(中位复发时间分别为8.5个月和17.1个月)。在多变量分析中，在C1后时间点的MRD状态独立地预测了生存，确定了一组预后特别差的中等风险患者。结论使用流式细胞术对老年AML患者的早期治疗反应评估提供了强大的独立预后信息，支持纳入MRD检测以完善风险分层，并为这一具有挑战性的患者组的临床试验设计提供支持。(C)美国临床肿瘤学会2013年
PurposeOlder patients with acute myeloid leukemia (AML) have a high relapse rate after standard chemotherapy. We investigated whether measuring chemotherapy sensitivity by multiparameter flow cytometric minimal residual disease (MFC-MRD) detection has prognostic value in patients older than age 60 years or is simply a surrogate for known age-related risk factors.Patient and MethodsEight hundred ninety-two unselected patients treated intensively in the United Kingdom National Cancer Research Institute AML16 Trial were assessed prospectively for MFC-MRD during treatment. Eight hundred thirty-three patients had leukemia-associated immunophenotypes (LAIPs) identified by pretreatment screening. Four hundred twenty-seven patients entered complete remission (CR) after one or two courses (designated C1 and C2, respectively) and were MFC-MRD assessable by LAIP detection in CR bone marrow for at least one of these time points. MRD positivity was defined as residual disease detectable by LAIP.ResultsMFC-MRD negativity, which was achieved in 51% of patients after C1 (n = 286) and 64% of patients after C2 (n = 279), conferred significantly better 3-year survival from CR (C1: 42% v 26% in MRD-positive patients, P < .001; C2: 38% v 18%, respectively; P < .001) and reduced relapse (C1: 71% v 83% in MRD-positive patients, P < .001; C2: 79% v 91%, respectively; P < .001), with higher risk of early relapse in MRD-positive patients (median time to relapse, 8.5 v 17.1 months, respectively). In multivariable analysis, MRD status at the post-C1 time point independently predicted survival, identifying a subgroup of intermediate-risk patients with particularly poor outcome. However, survival benefit from gemtuzumab ozogamicin was not associated with MFC-MRD chemotherapy sensitivity.ConclusionEarly assessment of treatment response using flow cytometry provides powerful independent prognostic information in older adults with AML, lending support to the incorporation of MRD detection to refine risk stratification and inform clinical trial design in this challenging group of patients. (C) 2013 by American Society of Clinical Oncology