Sylvie D. Freeman, University of Birmingham and University Hospitals Birmingham National Health Service (NHS) Trust, Birmingham; Paul Virgo, North Bristol NHS Trust, Bristol; Steve Couzens, University Hospital of Wales; Robert K. Hills and Alan K. Burnett, Cardiff University, Heath Park, Cardiff; David Grimwade, King's College London School of Medicine and Guy's and St Thomas' NHS Foundation Trust, London; and Nigel Russell, Nottingham University Hospital NHS Trust, Nottingham, United Kingdom.
J Clin Oncol. 2013 Nov 10;31(32):4123-31. doi: 10.1200/JCO.2013.49.1753. Epub 2013 Sep 23.
Older 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.
Eight 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.
MFC-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.
Early 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.
接受标准化疗的老年急性髓系白血病（AML）患者复发率较高。我们研究了多参数流式细胞术微小残留病（MFC-MRD）检测对年龄大于 60 岁的患者是否具有预测价值，是否只是已知与年龄相关的危险因素的替代指标。
在英国国家癌症研究所 AML16 试验中，892 例未经选择的强化治疗患者前瞻性地进行了治疗期间的 MFC-MRD 评估。833 例患者在预处理筛查时具有白血病相关免疫表型（LAIP）。427 例患者在一个或两个疗程后进入完全缓解（CR）（分别命名为 C1 和 C2），并且至少在这些时间点中的一个时间点，通过 LAIP 检测在 CR 骨髓中可评估 MFC-MRD。MRD 阳性定义为可通过 LAIP 检测到残留疾病。
在 C1 后（n = 286）和 C2 后（n = 279）分别有 51%和 64%的患者达到 MFC-MRD 阴性，这显著改善了 CR 后的 3 年生存率（C1：MRD 阳性患者为 42%，MRD 阴性患者为 26%，P <.001；C2：MRD 阳性患者为 38%，MRD 阴性患者为 18%，分别为 P <.001），降低了复发率（C1：MRD 阳性患者为 71%，MRD 阴性患者为 83%，P <.001；C2：MRD 阳性患者为 79%，MRD 阴性患者为 91%，P <.001），MRD 阳性患者的早期复发风险更高（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，C1 后时间点的 MRD 状态独立预测了生存，确定了一组具有特别差预后的中间风险患者。然而，吉妥珠单抗奥佐米星的生存获益与 MFC-MRD 化疗敏感性无关。
使用流式细胞术早期评估治疗反应在老年 AML 患者中提供了强大的独立预后信息，支持将 MRD 检测纳入风险分层，为这组具有挑战性的患者提供临床试验设计信息。
