Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1 and FLT3-internal tandem duplication genotypes

Prajwal C. Boddu, Tapan M. Kadia, Guillermo Garcia-Manero, Jorge Cortes, Mansour Alfayez, Gautam Borthakur, Marina Konopleva, Elias J. Jabbour, Naval G. Daver, Courtney D. DiNardo, Kiran Naqvi, Musa Yilmaz, Nicholas J. Short, Sherry Pierce, Hagop M. Kantarjian, Farhad Ravandi

Research output: Contribution to journalArticle

Abstract

Background: The revised 2017 European LeukemiaNet (ELN) classification (ELN-2017) of acute myeloid leukemia (AML) divides patients into 3 prognostic risk categories, with additional factors such as the fms-like tyrosine kinase 3 (FLT3)–internal tandem duplication (ITD) allele ratio (AR) considered for risk stratification. To the best of the authors' knowledge, the prognostic usefulness of ELN-2017 in comparison with ELN-2010 in younger patients with AML has not been validated to date. Methods: The authors performed a retrospective study on patients aged <60 years who received idarubicin plus cytarabine (IA)–based induction chemotherapy for newly diagnosed AML. Results: According to ELN-2017 criteria, the number of patients in the favorable (Fav), intermediate (Int), and adverse (Adv) risk categories was 192 patients (27%), 331 patients (46%), and 192 patients (27%), respectively. Overall survival probabilities at 5 years in the Fav, Int, and Adv groups were 57%, 37%, and 18%, respectively. In comparison, the 5-year overall survival probabilities in the Fav (169 patients), intermediate (IR)-1 (80 patients), IR-2 (306 patients), and Adv (160 patients) ELN-2010 categories were 59%, 32%, 40%, and 14%, respectively. Although ELN-2010 historically distinguishes prognosis into IR-1 and IR-2 categories in younger patients, this difference was nullified in the current study cohort. When comparing patients with a low FLT3-ITD AR with those with a high FLT3-ITD AR, no significant differences in survival were noted among patients with nucleophosmin 1 (NPM1)-mutated AML (P =.28) or wild-type NPM1 (P =.35), and in those treated with IA alone (P =.79) or those treated with IA and a FLT3 inhibitor (P =.10). Conclusions: The ELN-2017 more accurately distinguishes prognosis in patients with newly diagnosed AML. The lack of prognostic significance for the FLT3-ITD AR needs further evaluation in different treatment settings.

Original languageEnglish (US)
Pages (from-to)1091-1100
Number of pages10
JournalCancer
Volume125
Issue number7
DOIs
StatePublished - Apr 1 2019
Externally publishedYes

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fms-Like Tyrosine Kinase 3
Acute Myeloid Leukemia
Genotype
Alleles
nucleophosmin
Survival
Idarubicin
Induction Chemotherapy

Keywords

  • acute myeloid leukemia
  • allele ratio
  • European LeukemiaNet
  • prognosis
  • validation
  • younger

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1 and FLT3-internal tandem duplication genotypes. / Boddu, Prajwal C.; Kadia, Tapan M.; Garcia-Manero, Guillermo; Cortes, Jorge; Alfayez, Mansour; Borthakur, Gautam; Konopleva, Marina; Jabbour, Elias J.; Daver, Naval G.; DiNardo, Courtney D.; Naqvi, Kiran; Yilmaz, Musa; Short, Nicholas J.; Pierce, Sherry; Kantarjian, Hagop M.; Ravandi, Farhad.

In: Cancer, Vol. 125, No. 7, 01.04.2019, p. 1091-1100.

Research output: Contribution to journalArticle

Boddu, PC, Kadia, TM, Garcia-Manero, G, Cortes, J, Alfayez, M, Borthakur, G, Konopleva, M, Jabbour, EJ, Daver, NG, DiNardo, CD, Naqvi, K, Yilmaz, M, Short, NJ, Pierce, S, Kantarjian, HM & Ravandi, F 2019, 'Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1 and FLT3-internal tandem duplication genotypes', Cancer, vol. 125, no. 7, pp. 1091-1100. https://doi.org/10.1002/cncr.31885
Boddu, Prajwal C. ; Kadia, Tapan M. ; Garcia-Manero, Guillermo ; Cortes, Jorge ; Alfayez, Mansour ; Borthakur, Gautam ; Konopleva, Marina ; Jabbour, Elias J. ; Daver, Naval G. ; DiNardo, Courtney D. ; Naqvi, Kiran ; Yilmaz, Musa ; Short, Nicholas J. ; Pierce, Sherry ; Kantarjian, Hagop M. ; Ravandi, Farhad. / Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1 and FLT3-internal tandem duplication genotypes. In: Cancer. 2019 ; Vol. 125, No. 7. pp. 1091-1100.
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abstract = "Background: The revised 2017 European LeukemiaNet (ELN) classification (ELN-2017) of acute myeloid leukemia (AML) divides patients into 3 prognostic risk categories, with additional factors such as the fms-like tyrosine kinase 3 (FLT3)–internal tandem duplication (ITD) allele ratio (AR) considered for risk stratification. To the best of the authors' knowledge, the prognostic usefulness of ELN-2017 in comparison with ELN-2010 in younger patients with AML has not been validated to date. Methods: The authors performed a retrospective study on patients aged <60 years who received idarubicin plus cytarabine (IA)–based induction chemotherapy for newly diagnosed AML. Results: According to ELN-2017 criteria, the number of patients in the favorable (Fav), intermediate (Int), and adverse (Adv) risk categories was 192 patients (27{\%}), 331 patients (46{\%}), and 192 patients (27{\%}), respectively. Overall survival probabilities at 5 years in the Fav, Int, and Adv groups were 57{\%}, 37{\%}, and 18{\%}, respectively. In comparison, the 5-year overall survival probabilities in the Fav (169 patients), intermediate (IR)-1 (80 patients), IR-2 (306 patients), and Adv (160 patients) ELN-2010 categories were 59{\%}, 32{\%}, 40{\%}, and 14{\%}, respectively. Although ELN-2010 historically distinguishes prognosis into IR-1 and IR-2 categories in younger patients, this difference was nullified in the current study cohort. When comparing patients with a low FLT3-ITD AR with those with a high FLT3-ITD AR, no significant differences in survival were noted among patients with nucleophosmin 1 (NPM1)-mutated AML (P =.28) or wild-type NPM1 (P =.35), and in those treated with IA alone (P =.79) or those treated with IA and a FLT3 inhibitor (P =.10). Conclusions: The ELN-2017 more accurately distinguishes prognosis in patients with newly diagnosed AML. The lack of prognostic significance for the FLT3-ITD AR needs further evaluation in different treatment settings.",
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T1 - Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1 and FLT3-internal tandem duplication genotypes

AU - Boddu, Prajwal C.

AU - Kadia, Tapan M.

AU - Garcia-Manero, Guillermo

AU - Cortes, Jorge

AU - Alfayez, Mansour

AU - Borthakur, Gautam

AU - Konopleva, Marina

AU - Jabbour, Elias J.

AU - Daver, Naval G.

AU - DiNardo, Courtney D.

AU - Naqvi, Kiran

AU - Yilmaz, Musa

AU - Short, Nicholas J.

AU - Pierce, Sherry

AU - Kantarjian, Hagop M.

AU - Ravandi, Farhad

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Background: The revised 2017 European LeukemiaNet (ELN) classification (ELN-2017) of acute myeloid leukemia (AML) divides patients into 3 prognostic risk categories, with additional factors such as the fms-like tyrosine kinase 3 (FLT3)–internal tandem duplication (ITD) allele ratio (AR) considered for risk stratification. To the best of the authors' knowledge, the prognostic usefulness of ELN-2017 in comparison with ELN-2010 in younger patients with AML has not been validated to date. Methods: The authors performed a retrospective study on patients aged <60 years who received idarubicin plus cytarabine (IA)–based induction chemotherapy for newly diagnosed AML. Results: According to ELN-2017 criteria, the number of patients in the favorable (Fav), intermediate (Int), and adverse (Adv) risk categories was 192 patients (27%), 331 patients (46%), and 192 patients (27%), respectively. Overall survival probabilities at 5 years in the Fav, Int, and Adv groups were 57%, 37%, and 18%, respectively. In comparison, the 5-year overall survival probabilities in the Fav (169 patients), intermediate (IR)-1 (80 patients), IR-2 (306 patients), and Adv (160 patients) ELN-2010 categories were 59%, 32%, 40%, and 14%, respectively. Although ELN-2010 historically distinguishes prognosis into IR-1 and IR-2 categories in younger patients, this difference was nullified in the current study cohort. When comparing patients with a low FLT3-ITD AR with those with a high FLT3-ITD AR, no significant differences in survival were noted among patients with nucleophosmin 1 (NPM1)-mutated AML (P =.28) or wild-type NPM1 (P =.35), and in those treated with IA alone (P =.79) or those treated with IA and a FLT3 inhibitor (P =.10). Conclusions: The ELN-2017 more accurately distinguishes prognosis in patients with newly diagnosed AML. The lack of prognostic significance for the FLT3-ITD AR needs further evaluation in different treatment settings.

AB - Background: The revised 2017 European LeukemiaNet (ELN) classification (ELN-2017) of acute myeloid leukemia (AML) divides patients into 3 prognostic risk categories, with additional factors such as the fms-like tyrosine kinase 3 (FLT3)–internal tandem duplication (ITD) allele ratio (AR) considered for risk stratification. To the best of the authors' knowledge, the prognostic usefulness of ELN-2017 in comparison with ELN-2010 in younger patients with AML has not been validated to date. Methods: The authors performed a retrospective study on patients aged <60 years who received idarubicin plus cytarabine (IA)–based induction chemotherapy for newly diagnosed AML. Results: According to ELN-2017 criteria, the number of patients in the favorable (Fav), intermediate (Int), and adverse (Adv) risk categories was 192 patients (27%), 331 patients (46%), and 192 patients (27%), respectively. Overall survival probabilities at 5 years in the Fav, Int, and Adv groups were 57%, 37%, and 18%, respectively. In comparison, the 5-year overall survival probabilities in the Fav (169 patients), intermediate (IR)-1 (80 patients), IR-2 (306 patients), and Adv (160 patients) ELN-2010 categories were 59%, 32%, 40%, and 14%, respectively. Although ELN-2010 historically distinguishes prognosis into IR-1 and IR-2 categories in younger patients, this difference was nullified in the current study cohort. When comparing patients with a low FLT3-ITD AR with those with a high FLT3-ITD AR, no significant differences in survival were noted among patients with nucleophosmin 1 (NPM1)-mutated AML (P =.28) or wild-type NPM1 (P =.35), and in those treated with IA alone (P =.79) or those treated with IA and a FLT3 inhibitor (P =.10). Conclusions: The ELN-2017 more accurately distinguishes prognosis in patients with newly diagnosed AML. The lack of prognostic significance for the FLT3-ITD AR needs further evaluation in different treatment settings.

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KW - European LeukemiaNet

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