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

doi: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

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 journal › Article › peer-review

43 Scopus citations

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 language	English (US)
Pages (from-to)	1367-1374
Number of pages	8
Journal	Leukemia Research
Volume	39
Issue number	12
DOIs	https://doi.org/10.1016/j.leukres.2015.10.005
State	Published - 2015
Externally published	Yes

Keywords

AML
FLT3-ITD
Leukemic transformation
MDS
RAS

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.leukres.2015.10.005

Cite this

Badar, T., Patel, K. P., Thompson, P. A., DiNardo, C., Takahashi, K., Cabrero, M., Borthakur, G., Cortes, J., Konopleva, M., Kadia, T., Bohannan, Z., Pierce, S., Jabbour, E. J., 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, 39(12), 1367-1374. https://doi.org/10.1016/j.leukres.2015.10.005

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

@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",

note = "Funding Information: MC-C is funded by the Fundacion Alfonso Martin-Escudero. GGM is supported by the by MD Anderson Cancer Center Support Grant P30CA016672. GGM is also supported by the Edward P. Evans Foundation, the Fundacion Ramon Areces, grant RP100202 from the Cancer Prevention & Research Institute of Texas (CPRIT), and by generous philanthropic contributions to MD Anderson's MDS/AML Moon Shot Program . GGM partially supported by the Dr. Kenneth B. McCredie Chair in Clinical Leukemia Research endowment. Funding Information: This work was supported by The University of Texas MD Anderson Cancer Center Support Grant CA016672, Edward P. Evans Foundation, the Fundacion Ramon Areces, grant RP100202 from the Cancer Prevention & Research Institute of Texas (CPRIT), and philanthropic contributions to MD Anderson{\textquoteright}s MDS/AML Moon Shot Program . Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd.",

year = "2015",

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

N1 - Funding Information: MC-C is funded by the Fundacion Alfonso Martin-Escudero. GGM is supported by the by MD Anderson Cancer Center Support Grant P30CA016672. GGM is also supported by the Edward P. Evans Foundation, the Fundacion Ramon Areces, grant RP100202 from the Cancer Prevention & Research Institute of Texas (CPRIT), and by generous philanthropic contributions to MD Anderson's MDS/AML Moon Shot Program . GGM partially supported by the Dr. Kenneth B. McCredie Chair in Clinical Leukemia Research endowment. Funding Information: This work was supported by The University of Texas MD Anderson Cancer Center Support Grant CA016672, Edward P. Evans Foundation, the Fundacion Ramon Areces, grant RP100202 from the Cancer Prevention & Research Institute of Texas (CPRIT), and philanthropic contributions to MD Anderson’s MDS/AML Moon Shot Program . Publisher Copyright: © 2015 Elsevier Ltd.

PY - 2015

Y1 - 2015

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

SN - 0145-2126

VL - 39

SP - 1367

EP - 1374

JO - Leukemia Research

JF - Leukemia Research

IS - 12

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this