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

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.

• Authors: Farhad Ravandi, Jeffrey Jorgensen, Gautam Borthakur, Elias Jabbour, Tapan Kadia, Sherry Pierce, Mark Brandt, Sa Wang, Sergej Konoplev, Xuemei Wang, Xuelin Huang, Naval Daver, Courtney DiNardo, Michael Andreeff, Marina Konopleva, Zeev Estrov, Guillermo Garcia-Manero, Jorge Cortes, Hagop Kantarjian
• Journal: Cancer (Cancer) Vol. 123 Issue 3 Pg. 426-435 (02 01 2017) ISSN: 1097-0142 [Electronic] United States
• PMID: 27657543 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2016 American Cancer Society.

Chemical References

• Cytarabine
• Idarubicin

Topics

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