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Persistence of minimal residual disease assessed by multiparameter flow cytometry is highly prognostic in younger patients with acute myeloid leukemia
Author(s) -
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,
GarciaManero Guillermo,
Cortes Jorge,
Kantarjian Hagop
Publication year - 2017
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.30361
Subject(s) - medicine , minimal residual disease , idarubicin , cytarabine , myeloid leukemia , oncology , gastroenterology , univariate analysis , multivariate analysis , leukemia , myeloid , induction chemotherapy , chemotherapy , surgery
BACKGROUND 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. METHODS Among 280 younger patients who were treated with intermediate‐dose cytarabine (total ≥ 5 g/m 2 ) 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. RESULTS 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). CONCLUSIONS 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 .