Persistence of minimal residual disease assessed by multiparameter flow cytometry is highly prognostic in younger patients with acute myeloid leukemia

Cancer. 2017 Feb 1;123(3):426-435. doi: 10.1002/cncr.30361. Epub 2016 Sep 22.

Abstract

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. © 2016 American Cancer Society.

Keywords: acute myeloid leukemia; minimal residual disease; prognostic; relapse-free survival; survival.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Disease-Free Survival
  • Female
  • Flow Cytometry
  • Humans
  • Idarubicin / administration & dosage
  • Idarubicin / adverse effects
  • Induction Chemotherapy / adverse effects*
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Neoplasm, Residual / chemically induced
  • Neoplasm, Residual / pathology*
  • Prognosis*
  • Remission Induction

Substances

  • Cytarabine
  • Idarubicin