Effect of NPM1 and FLT3 mutations on the outcomes of elderly patients with acute myeloid leukemia receiving standard chemotherapy

Naval Daver, Theresa Liu Dumlao, Farhad Ravandi, Sherry Pierce, Gautam Borthakur, Naveen Pemmaraju, Aziz Nazha, Stefan Faderl, Elias Jabbour, Guillermo Garcia-Manero, Jorges Cortes, Hagop Kantarjian, Alfonso Quintás-Cardama

Research output: Contribution to journalArticle

Abstract

Background: The effect of prognostically important gene mutations (MUTs), nucleophosmin (nucleolar phosphoprotein B23, numatrin) (NPM1) and fms-related tyrosine kinase 3 (FLT3), in elderly patients with acute myeloid leukemia (AML) is not well defined. Patients and Methods: We analyzed 557 patients, 65 years of age or older with newly diagnosed AML, treated at our institution between 2000 and 2010 with cytotoxic chemotherapy. NPM1 and FLT3 analysis were available in 146 patients (26%) and 388 patients (70%), respectively. Results: NPM1 and FLT3 MUTs occurred in 16% and 12% of patients, respectively. No difference in median overall survival was observed between FLT3-MUT and NPM1-MUT patients who received cytotoxic chemotherapy. Outcome was significantly better among patients with NPM1-MUT/FLT3-wild type (WT) genotype (n = 14) compared with patients carrying FLT3/NPM1 genotypes other than NPM1-MUT/FLT3-WT (n = 125). The complete remission rates were 71% and 49%, respectively (P =.11). The median survival was 21.5 months vs. 9.0 months and estimated 2-year survival rates were 51% vs. 38%, respectively (P =.003). NPM1 and FLT3 MUTs appear to occur less frequently in elderly AML patients. The prognostic effect of isolated NPM1- or isolated FLT3-MUT is minimal. Conclusion: Elderly AML patients with NPM1-MUT/FLT3-WT genotype have significantly improved outcomes compared with patients with other NPM1/FLT3 genotypes when treated with cytotoxic chemotherapy.

Original languageEnglish (US)
Pages (from-to)435-440
Number of pages6
JournalClinical Lymphoma, Myeloma and Leukemia
Volume13
Issue number4
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

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Acute Myeloid Leukemia
Drug Therapy
Mutation
Genotype
Survival
Protein-Tyrosine Kinases
Survival Rate

Keywords

  • Acute myeloid leukemia
  • Cytotoxic chemotherapy
  • Elderly
  • FLT3
  • NPM1

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Effect of NPM1 and FLT3 mutations on the outcomes of elderly patients with acute myeloid leukemia receiving standard chemotherapy. / Daver, Naval; Liu Dumlao, Theresa; Ravandi, Farhad; Pierce, Sherry; Borthakur, Gautam; Pemmaraju, Naveen; Nazha, Aziz; Faderl, Stefan; Jabbour, Elias; Garcia-Manero, Guillermo; Cortes, Jorges; Kantarjian, Hagop; Quintás-Cardama, Alfonso.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 13, No. 4, 01.08.2013, p. 435-440.

Research output: Contribution to journalArticle

Daver, N, Liu Dumlao, T, Ravandi, F, Pierce, S, Borthakur, G, Pemmaraju, N, Nazha, A, Faderl, S, Jabbour, E, Garcia-Manero, G, Cortes, J, Kantarjian, H & Quintás-Cardama, A 2013, 'Effect of NPM1 and FLT3 mutations on the outcomes of elderly patients with acute myeloid leukemia receiving standard chemotherapy', Clinical Lymphoma, Myeloma and Leukemia, vol. 13, no. 4, pp. 435-440. https://doi.org/10.1016/j.clml.2013.02.021
Daver, Naval ; Liu Dumlao, Theresa ; Ravandi, Farhad ; Pierce, Sherry ; Borthakur, Gautam ; Pemmaraju, Naveen ; Nazha, Aziz ; Faderl, Stefan ; Jabbour, Elias ; Garcia-Manero, Guillermo ; Cortes, Jorges ; Kantarjian, Hagop ; Quintás-Cardama, Alfonso. / Effect of NPM1 and FLT3 mutations on the outcomes of elderly patients with acute myeloid leukemia receiving standard chemotherapy. In: Clinical Lymphoma, Myeloma and Leukemia. 2013 ; Vol. 13, No. 4. pp. 435-440.
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abstract = "Background: The effect of prognostically important gene mutations (MUTs), nucleophosmin (nucleolar phosphoprotein B23, numatrin) (NPM1) and fms-related tyrosine kinase 3 (FLT3), in elderly patients with acute myeloid leukemia (AML) is not well defined. Patients and Methods: We analyzed 557 patients, 65 years of age or older with newly diagnosed AML, treated at our institution between 2000 and 2010 with cytotoxic chemotherapy. NPM1 and FLT3 analysis were available in 146 patients (26{\%}) and 388 patients (70{\%}), respectively. Results: NPM1 and FLT3 MUTs occurred in 16{\%} and 12{\%} of patients, respectively. No difference in median overall survival was observed between FLT3-MUT and NPM1-MUT patients who received cytotoxic chemotherapy. Outcome was significantly better among patients with NPM1-MUT/FLT3-wild type (WT) genotype (n = 14) compared with patients carrying FLT3/NPM1 genotypes other than NPM1-MUT/FLT3-WT (n = 125). The complete remission rates were 71{\%} and 49{\%}, respectively (P =.11). The median survival was 21.5 months vs. 9.0 months and estimated 2-year survival rates were 51{\%} vs. 38{\%}, respectively (P =.003). NPM1 and FLT3 MUTs appear to occur less frequently in elderly AML patients. The prognostic effect of isolated NPM1- or isolated FLT3-MUT is minimal. Conclusion: Elderly AML patients with NPM1-MUT/FLT3-WT genotype have significantly improved outcomes compared with patients with other NPM1/FLT3 genotypes when treated with cytotoxic chemotherapy.",
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T1 - Effect of NPM1 and FLT3 mutations on the outcomes of elderly patients with acute myeloid leukemia receiving standard chemotherapy

AU - Daver, Naval

AU - Liu Dumlao, Theresa

AU - Ravandi, Farhad

AU - Pierce, Sherry

AU - Borthakur, Gautam

AU - Pemmaraju, Naveen

AU - Nazha, Aziz

AU - Faderl, Stefan

AU - Jabbour, Elias

AU - Garcia-Manero, Guillermo

AU - Cortes, Jorges

AU - Kantarjian, Hagop

AU - Quintás-Cardama, Alfonso

PY - 2013/8/1

Y1 - 2013/8/1

N2 - Background: The effect of prognostically important gene mutations (MUTs), nucleophosmin (nucleolar phosphoprotein B23, numatrin) (NPM1) and fms-related tyrosine kinase 3 (FLT3), in elderly patients with acute myeloid leukemia (AML) is not well defined. Patients and Methods: We analyzed 557 patients, 65 years of age or older with newly diagnosed AML, treated at our institution between 2000 and 2010 with cytotoxic chemotherapy. NPM1 and FLT3 analysis were available in 146 patients (26%) and 388 patients (70%), respectively. Results: NPM1 and FLT3 MUTs occurred in 16% and 12% of patients, respectively. No difference in median overall survival was observed between FLT3-MUT and NPM1-MUT patients who received cytotoxic chemotherapy. Outcome was significantly better among patients with NPM1-MUT/FLT3-wild type (WT) genotype (n = 14) compared with patients carrying FLT3/NPM1 genotypes other than NPM1-MUT/FLT3-WT (n = 125). The complete remission rates were 71% and 49%, respectively (P =.11). The median survival was 21.5 months vs. 9.0 months and estimated 2-year survival rates were 51% vs. 38%, respectively (P =.003). NPM1 and FLT3 MUTs appear to occur less frequently in elderly AML patients. The prognostic effect of isolated NPM1- or isolated FLT3-MUT is minimal. Conclusion: Elderly AML patients with NPM1-MUT/FLT3-WT genotype have significantly improved outcomes compared with patients with other NPM1/FLT3 genotypes when treated with cytotoxic chemotherapy.

AB - Background: The effect of prognostically important gene mutations (MUTs), nucleophosmin (nucleolar phosphoprotein B23, numatrin) (NPM1) and fms-related tyrosine kinase 3 (FLT3), in elderly patients with acute myeloid leukemia (AML) is not well defined. Patients and Methods: We analyzed 557 patients, 65 years of age or older with newly diagnosed AML, treated at our institution between 2000 and 2010 with cytotoxic chemotherapy. NPM1 and FLT3 analysis were available in 146 patients (26%) and 388 patients (70%), respectively. Results: NPM1 and FLT3 MUTs occurred in 16% and 12% of patients, respectively. No difference in median overall survival was observed between FLT3-MUT and NPM1-MUT patients who received cytotoxic chemotherapy. Outcome was significantly better among patients with NPM1-MUT/FLT3-wild type (WT) genotype (n = 14) compared with patients carrying FLT3/NPM1 genotypes other than NPM1-MUT/FLT3-WT (n = 125). The complete remission rates were 71% and 49%, respectively (P =.11). The median survival was 21.5 months vs. 9.0 months and estimated 2-year survival rates were 51% vs. 38%, respectively (P =.003). NPM1 and FLT3 MUTs appear to occur less frequently in elderly AML patients. The prognostic effect of isolated NPM1- or isolated FLT3-MUT is minimal. Conclusion: Elderly AML patients with NPM1-MUT/FLT3-WT genotype have significantly improved outcomes compared with patients with other NPM1/FLT3 genotypes when treated with cytotoxic chemotherapy.

KW - Acute myeloid leukemia

KW - Cytotoxic chemotherapy

KW - Elderly

KW - FLT3

KW - NPM1

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