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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)426-435
Number of pages10
JournalCancer
Volume123
Issue number3
DOIs
StatePublished - Feb 1 2017
Externally publishedYes

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Residual Neoplasm
Acute Myeloid Leukemia
Flow Cytometry
Idarubicin
Cytarabine
Induction Chemotherapy
Survival
Cytogenetics
Blood Platelets
Multivariate Analysis
Color
Bone Marrow
Recurrence

Keywords

  • acute myeloid leukemia
  • minimal residual disease
  • prognostic
  • relapse-free survival
  • survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ravandi, F., Jorgensen, J., Borthakur, G., Jabbour, E., Kadia, T., Pierce, S., ... Kantarjian, H. (2017). Persistence of minimal residual disease assessed by multiparameter flow cytometry is highly prognostic in younger patients with acute myeloid leukemia. Cancer, 123(3), 426-435. https://doi.org/10.1002/cncr.30361

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

In: Cancer, Vol. 123, No. 3, 01.02.2017, p. 426-435.

Research output: Contribution to journalArticle

Ravandi, F, Jorgensen, J, Borthakur, G, Jabbour, E, Kadia, T, Pierce, S, Brandt, M, Wang, S, Konoplev, S, Wang, X, Huang, X, Daver, N, DiNardo, C, Andreeff, M, Konopleva, M, Estrov, Z, Garcia-Manero, G, Cortes, J & Kantarjian, H 2017, 'Persistence of minimal residual disease assessed by multiparameter flow cytometry is highly prognostic in younger patients with acute myeloid leukemia', Cancer, vol. 123, no. 3, pp. 426-435. https://doi.org/10.1002/cncr.30361
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. / Persistence of minimal residual disease assessed by multiparameter flow cytometry is highly prognostic in younger patients with acute myeloid leukemia. In: Cancer. 2017 ; Vol. 123, No. 3. pp. 426-435.
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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.",
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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

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.

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