TY - JOUR
T1 - Persistence of minimal residual disease assessed by multiparameter flow cytometry is highly prognostic in younger patients with acute myeloid leukemia
AU - Ravandi, Farhad
AU - Jorgensen, Jeffrey
AU - Borthakur, Gautam
AU - Jabbour, Elias
AU - Kadia, Tapan
AU - Pierce, Sherry
AU - Brandt, Mark
AU - Wang, Sa
AU - Konoplev, Sergej
AU - Wang, Xuemei
AU - Huang, Xuelin
AU - Daver, Naval
AU - DiNardo, Courtney
AU - Andreeff, Michael
AU - Konopleva, Marina
AU - Estrov, Zeev
AU - Garcia-Manero, Guillermo
AU - Cortes, Jorge
AU - Kantarjian, Hagop
N1 - Publisher Copyright:
© 2016 American Cancer Society
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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/m2) 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.
AB - 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/m2) 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.
KW - acute myeloid leukemia
KW - minimal residual disease
KW - prognostic
KW - relapse-free survival
KW - survival
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U2 - 10.1002/cncr.30361
DO - 10.1002/cncr.30361
M3 - Article
C2 - 27657543
AN - SCOPUS:85010670247
SN - 0008-543X
VL - 123
SP - 426
EP - 435
JO - Cancer
JF - Cancer
IS - 3
ER -
