Ravandi Farhad, Jorgensen Jeffrey, Borthakur Gautam, Jabbour Elias, Kadia Tapan, Pierce Sherry, Brandt Mark, Wang Sa, Konoplev Sergej, Wang Xuemei, Huang Xuelin, Daver Naval, DiNardo Courtney, Andreeff Michael, Konopleva Marina, Estrov Zeev, Garcia-Manero Guillermo, Cortes Jorge, Kantarjian Hagop
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer. 2017 Feb 1;123(3):426-435. doi: 10.1002/cncr.30361. Epub 2016 Sep 22.
Predicting outcomes for patients with acute myeloid leukemia (AML) on the basis of pretreatment predictors has been the cornerstone of management. Posttreatment prognostic factors are increasingly being evaluated.
Among 280 younger patients who were treated with intermediate-dose cytarabine (total ≥ 5 g/m ) and idarubicin-based induction chemotherapy and achieved remission, 186 were assessed for minimal residual disease (MRD) with an 8-color multiparameter flow cytometry panel performed on bone marrow specimens with a sensitivity of 0.1% or higher.
One hundred sixty-six patients had samples available 1 to 2 months after induction at the time of complete remission (CR), and 79% became negative for MRD, with an MRD-negative status associated with an improvement in relapse-free survival (RFS; P = .0002) and overall survival (OS; P = .0002). One hundred sixteen were evaluated for their MRD status during consolidation, and 86% were negative, with an MRD-negative status associated with a significant improvement in RFS (P < .0001) and OS (P < .0001). Sixty-nine patients were evaluated for their MRD status after completion of all therapy, and 84% were negative, with an MRD-negative status associated with an improvement in RFS (P < .0001) and OS (P < .0001). In a multivariate analysis including age, cytogenetics, response (CR vs CR with incomplete platelet recovery/incomplete blood count recovery), and MRD, achieving an MRD-negative status was the most important independent predictor of RFS and OS at response (P = .008 and P = .0008, respectively), during consolidation (P < .0001 for both), and at the completion of therapy (P < .0001 and P = .002, respectively).
Achieving an MRD-negative status according to multiparameter flow cytometry is associated with a highly significant improvement in the outcomes of younger patients with AML receiving cytosine arabinoside plus idarubicin-based induction and consolidation regimens. Cancer 2017;123:426-435. © 2016 American Cancer Society.
基于预处理预测指标来预测急性髓系白血病(AML)患者的预后一直是治疗的基石。目前对治疗后预后因素的评估越来越多。
在280例接受中剂量阿糖胞苷(总量≥5g/m²)和基于伊达比星的诱导化疗并获得缓解的年轻患者中,186例通过对骨髓标本进行8色多参数流式细胞术检测来评估微小残留病(MRD),检测灵敏度为0.1%或更高。
166例患者在诱导后1至2个月完全缓解(CR)时可获得样本,79%的患者MRD转为阴性,MRD阴性状态与无复发生存期(RFS;P = 0.0002)和总生存期(OS;P = 0.0002)的改善相关。116例患者在巩固治疗期间评估了MRD状态,86%为阴性,MRD阴性状态与RFS(P < 0.0001)和OS(P < 0.0001)的显著改善相关。69例患者在所有治疗完成后评估了MRD状态,84%为阴性,MRD阴性状态与RFS(P < 0.0001)和OS(P < 0.0001)的改善相关。在一项包括年龄、细胞遗传学、缓解情况(CR与血小板恢复不完全/血细胞计数恢复不完全的CR)和MRD的多变量分析中,达到MRD阴性状态是缓解时(分别为P = 0.008和P = 0.0008)、巩固治疗期间(两者均为P < 0.0001)以及治疗完成时(分别为P < 0.0001和P = 0.002)RFS和OS的最重要独立预测因素。
对于接受阿糖胞苷加伊达比星诱导和巩固方案治疗的年轻AML患者,通过多参数流式细胞术达到MRD阴性状态与预后的显著改善相关。《癌症》2017年;123:426 - 435。© 2016美国癌症协会