Detectable FLT3-ITD or RAS mutation at the time of transformation from MDS to AML predicts for very poor outcomes

Talha Badar, Keyur P. Patel, Philip A. Thompson, Courtney DiNardo, Koichi Takahashi, Monica Cabrero, Gautam Borthakur, Jorge Cortes, Marina Konopleva, Tapan Kadia, Zach Bohannan, Sherry Pierce, Elias J. Jabbour, Farhad Ravandi, Naval Daver, Raja Luthra, Hagop Kantarjian, Guillermo Garcia-Manero

Research output: Contribution to journalArticle

Abstract

Background: The molecular events that drive the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML) have yet to be fully characterized. We hypothesized that detection of these mutations at the time of transformation from MDS to AML may lead to poorer outcomes. Methods: We analyzed 102 MDS patients who were admitted to our institution between 2004 and 2013, had wild-type (wt) FLT3-ITD and RAS at diagnosis, progressed to AML, and had serial mutation testing at both the MDS and AML stages. Results: We detected FLT3-ITD and/or RAS mutations in twenty-seven (26%) patients at the time of transformation to AML. Twenty-two patients (81%) had RAS mutations and five (19%) had FLT3-ITD mutations. The median survival after leukemia transformation in patients who had detectable RAS and/or FLT3-ITD mutations was 2.4 months compared to 7.5 months in patients who retained wt RAS and FLT3-ITD (hazard ratio [HR]: 3.08, 95% confidence interval [CI]: 1.9-5.0, p < 0.0001). In multivariate analysis, FLT3-ITD and RAS mutations had independent prognostic significance for poor outcome.

Original languageEnglish (US)
Pages (from-to)1367-1374
Number of pages8
JournalLeukemia Research
Volume39
Issue number12
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Myelodysplastic Syndromes
Acute Myeloid Leukemia
Mutation
Leukemia
Multivariate Analysis
Confidence Intervals
Survival

Keywords

  • AML
  • FLT3-ITD
  • Leukemic transformation
  • MDS
  • RAS

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Badar, T., Patel, K. P., Thompson, P. A., DiNardo, C., Takahashi, K., Cabrero, M., ... Garcia-Manero, G. (2015). Detectable FLT3-ITD or RAS mutation at the time of transformation from MDS to AML predicts for very poor outcomes. Leukemia Research, 39(12), 1367-1374. https://doi.org/10.1016/j.leukres.2015.10.005

Detectable FLT3-ITD or RAS mutation at the time of transformation from MDS to AML predicts for very poor outcomes. / Badar, Talha; Patel, Keyur P.; Thompson, Philip A.; DiNardo, Courtney; Takahashi, Koichi; Cabrero, Monica; Borthakur, Gautam; Cortes, Jorge; Konopleva, Marina; Kadia, Tapan; Bohannan, Zach; Pierce, Sherry; Jabbour, Elias J.; Ravandi, Farhad; Daver, Naval; Luthra, Raja; Kantarjian, Hagop; Garcia-Manero, Guillermo.

In: Leukemia Research, Vol. 39, No. 12, 01.01.2015, p. 1367-1374.

Research output: Contribution to journalArticle

Badar, T, Patel, KP, Thompson, PA, DiNardo, C, Takahashi, K, Cabrero, M, Borthakur, G, Cortes, J, Konopleva, M, Kadia, T, Bohannan, Z, Pierce, S, Jabbour, EJ, Ravandi, F, Daver, N, Luthra, R, Kantarjian, H & Garcia-Manero, G 2015, 'Detectable FLT3-ITD or RAS mutation at the time of transformation from MDS to AML predicts for very poor outcomes', Leukemia Research, vol. 39, no. 12, pp. 1367-1374. https://doi.org/10.1016/j.leukres.2015.10.005
Badar, Talha ; Patel, Keyur P. ; Thompson, Philip A. ; DiNardo, Courtney ; Takahashi, Koichi ; Cabrero, Monica ; Borthakur, Gautam ; Cortes, Jorge ; Konopleva, Marina ; Kadia, Tapan ; Bohannan, Zach ; Pierce, Sherry ; Jabbour, Elias J. ; Ravandi, Farhad ; Daver, Naval ; Luthra, Raja ; Kantarjian, Hagop ; Garcia-Manero, Guillermo. / Detectable FLT3-ITD or RAS mutation at the time of transformation from MDS to AML predicts for very poor outcomes. In: Leukemia Research. 2015 ; Vol. 39, No. 12. pp. 1367-1374.
@article{581dab352d4a41aca60758d4b833aa7f,
title = "Detectable FLT3-ITD or RAS mutation at the time of transformation from MDS to AML predicts for very poor outcomes",
abstract = "Background: The molecular events that drive the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML) have yet to be fully characterized. We hypothesized that detection of these mutations at the time of transformation from MDS to AML may lead to poorer outcomes. Methods: We analyzed 102 MDS patients who were admitted to our institution between 2004 and 2013, had wild-type (wt) FLT3-ITD and RAS at diagnosis, progressed to AML, and had serial mutation testing at both the MDS and AML stages. Results: We detected FLT3-ITD and/or RAS mutations in twenty-seven (26{\%}) patients at the time of transformation to AML. Twenty-two patients (81{\%}) had RAS mutations and five (19{\%}) had FLT3-ITD mutations. The median survival after leukemia transformation in patients who had detectable RAS and/or FLT3-ITD mutations was 2.4 months compared to 7.5 months in patients who retained wt RAS and FLT3-ITD (hazard ratio [HR]: 3.08, 95{\%} confidence interval [CI]: 1.9-5.0, p < 0.0001). In multivariate analysis, FLT3-ITD and RAS mutations had independent prognostic significance for poor outcome.",
keywords = "AML, FLT3-ITD, Leukemic transformation, MDS, RAS",
author = "Talha Badar and Patel, {Keyur P.} and Thompson, {Philip A.} and Courtney DiNardo and Koichi Takahashi and Monica Cabrero and Gautam Borthakur and Jorge Cortes and Marina Konopleva and Tapan Kadia and Zach Bohannan and Sherry Pierce and Jabbour, {Elias J.} and Farhad Ravandi and Naval Daver and Raja Luthra and Hagop Kantarjian and Guillermo Garcia-Manero",
year = "2015",
month = "1",
day = "1",
doi = "10.1016/j.leukres.2015.10.005",
language = "English (US)",
volume = "39",
pages = "1367--1374",
journal = "Leukemia Research",
issn = "0145-2126",
publisher = "Elsevier Limited",
number = "12",

}

TY - JOUR

T1 - Detectable FLT3-ITD or RAS mutation at the time of transformation from MDS to AML predicts for very poor outcomes

AU - Badar, Talha

AU - Patel, Keyur P.

AU - Thompson, Philip A.

AU - DiNardo, Courtney

AU - Takahashi, Koichi

AU - Cabrero, Monica

AU - Borthakur, Gautam

AU - Cortes, Jorge

AU - Konopleva, Marina

AU - Kadia, Tapan

AU - Bohannan, Zach

AU - Pierce, Sherry

AU - Jabbour, Elias J.

AU - Ravandi, Farhad

AU - Daver, Naval

AU - Luthra, Raja

AU - Kantarjian, Hagop

AU - Garcia-Manero, Guillermo

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background: The molecular events that drive the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML) have yet to be fully characterized. We hypothesized that detection of these mutations at the time of transformation from MDS to AML may lead to poorer outcomes. Methods: We analyzed 102 MDS patients who were admitted to our institution between 2004 and 2013, had wild-type (wt) FLT3-ITD and RAS at diagnosis, progressed to AML, and had serial mutation testing at both the MDS and AML stages. Results: We detected FLT3-ITD and/or RAS mutations in twenty-seven (26%) patients at the time of transformation to AML. Twenty-two patients (81%) had RAS mutations and five (19%) had FLT3-ITD mutations. The median survival after leukemia transformation in patients who had detectable RAS and/or FLT3-ITD mutations was 2.4 months compared to 7.5 months in patients who retained wt RAS and FLT3-ITD (hazard ratio [HR]: 3.08, 95% confidence interval [CI]: 1.9-5.0, p < 0.0001). In multivariate analysis, FLT3-ITD and RAS mutations had independent prognostic significance for poor outcome.

AB - Background: The molecular events that drive the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML) have yet to be fully characterized. We hypothesized that detection of these mutations at the time of transformation from MDS to AML may lead to poorer outcomes. Methods: We analyzed 102 MDS patients who were admitted to our institution between 2004 and 2013, had wild-type (wt) FLT3-ITD and RAS at diagnosis, progressed to AML, and had serial mutation testing at both the MDS and AML stages. Results: We detected FLT3-ITD and/or RAS mutations in twenty-seven (26%) patients at the time of transformation to AML. Twenty-two patients (81%) had RAS mutations and five (19%) had FLT3-ITD mutations. The median survival after leukemia transformation in patients who had detectable RAS and/or FLT3-ITD mutations was 2.4 months compared to 7.5 months in patients who retained wt RAS and FLT3-ITD (hazard ratio [HR]: 3.08, 95% confidence interval [CI]: 1.9-5.0, p < 0.0001). In multivariate analysis, FLT3-ITD and RAS mutations had independent prognostic significance for poor outcome.

KW - AML

KW - FLT3-ITD

KW - Leukemic transformation

KW - MDS

KW - RAS

UR - http://www.scopus.com/inward/record.url?scp=84961711374&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961711374&partnerID=8YFLogxK

U2 - 10.1016/j.leukres.2015.10.005

DO - 10.1016/j.leukres.2015.10.005

M3 - Article

C2 - 26547258

AN - SCOPUS:84961711374

VL - 39

SP - 1367

EP - 1374

JO - Leukemia Research

JF - Leukemia Research

SN - 0145-2126

IS - 12

ER -