Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML

Kamal Menghrajani; Alexandra Gomez-Arteaga; Rafael Madero-Marroquin; Mei Jie Zhang; Khalid Bo-Subait; Jonathan Sanchez; Hai Lin Wang; Mahmoud Aljurf; Amer Assal; Vera Ulrike Bacher; Sherif M. Badawy; Nelli Bejanyan; Vijaya Raj Bhatt; Christopher Bredeson; Michael Byrne; Paul Castillo; Jan Cerny; Saurabh Chhabra; Stefan Octavian Ciurea; Zachariah DeFilipp; Nosha Farhadfar; Shahinaz Gadalla; Robert Peter Gale; Siddhartha Ganguly; Lohith Gowda; Michael R. Grunwald; Shahrukh Hashmi; Gerhard Hildebrandt; Christopher G. Kanakry; Ankit Kansagra; Farhad Khimani; Maxwell Krem; Hillard Lazarus; Hongtao Liu; Rodrigo Martino; Fotios V. Michelis; Sunita Nathan; Taiga Nishihori; Richard Olsson; Ran Reshef; David Rizzieri; Jacob M. Rowe; Bipin N. Savani; Sachiko Seo; Akshay Sharma; Melhem Solh; Celalettin Ustun; Leo F. Verdonck; Christopher Hourigan; Brenda Sandmaier; Mark Litzow; Partow Kebriaei; Daniel Weisdorf; Yanming Zhang; Martin S. Tallman; Wael Saber

doi:10.1182/bloodadvances.2021004881

Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML

Kamal Menghrajani^*, Alexandra Gomez-Arteaga, Rafael Madero-Marroquin, Mei Jie Zhang, Khalid Bo-Subait, Jonathan Sanchez, Hai Lin Wang, Mahmoud Aljurf, Amer Assal, Vera Ulrike Bacher, Sherif M. Badawy, Nelli Bejanyan, Vijaya Raj Bhatt, Christopher Bredeson, Michael Byrne, Paul Castillo, Jan Cerny, Saurabh Chhabra, Stefan Octavian Ciurea, Zachariah DeFilippNosha Farhadfar, Shahinaz Gadalla, Robert Peter Gale, Siddhartha Ganguly, Lohith Gowda, Michael R. Grunwald, Shahrukh Hashmi, Gerhard Hildebrandt, Christopher G. Kanakry, Ankit Kansagra, Farhad Khimani, Maxwell Krem, Hillard Lazarus, Hongtao Liu, Rodrigo Martino, Fotios V. Michelis, Sunita Nathan, Taiga Nishihori, Richard Olsson, Ran Reshef, David Rizzieri, Jacob M. Rowe, Bipin N. Savani, Sachiko Seo, Akshay Sharma, Melhem Solh, Celalettin Ustun, Leo F. Verdonck, Christopher Hourigan, Brenda Sandmaier, Mark Litzow, Partow Kebriaei, Daniel Weisdorf, Yanming Zhang, Martin S. Tallman, Wael Saber

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P 5 .01; HR, 1.71; P , .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P 5 .002, and HR, 1.47; P , .001), as was overall survival (HR, 1.32; P , .001, and HR, 1.45; P , .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.

Original language	English (US)
Pages (from-to)	828-847
Number of pages	20
Journal	Blood Advances
Volume	6
Issue number	3
DOIs	https://doi.org/10.1182/bloodadvances.2021004881
State	Published - Feb 8 2022

ASJC Scopus subject areas

Hematology

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10.1182/bloodadvances.2021004881

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Menghrajani, K., Gomez-Arteaga, A., Madero-Marroquin, R., Zhang, M. J., Bo-Subait, K., Sanchez, J., Wang, H. L., Aljurf, M., Assal, A., Bacher, V. U., Badawy, S. M., Bejanyan, N., Bhatt, V. R., Bredeson, C., Byrne, M., Castillo, P., Cerny, J., Chhabra, S., Ciurea, S. O., ... Saber, W. (2022). Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML. Blood Advances, 6(3), 828-847. https://doi.org/10.1182/bloodadvances.2021004881

@article{e8e1f634e93b429b9c3ef97a1dbd5876,

title = "Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML",

abstract = "Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P 5 .01; HR, 1.71; P , .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P 5 .002, and HR, 1.47; P , .001), as was overall survival (HR, 1.32; P , .001, and HR, 1.45; P , .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.",

author = "Kamal Menghrajani and Alexandra Gomez-Arteaga and Rafael Madero-Marroquin and Zhang, {Mei Jie} and Khalid Bo-Subait and Jonathan Sanchez and Wang, {Hai Lin} and Mahmoud Aljurf and Amer Assal and Bacher, {Vera Ulrike} and Badawy, {Sherif M.} and Nelli Bejanyan and Bhatt, {Vijaya Raj} and Christopher Bredeson and Michael Byrne and Paul Castillo and Jan Cerny and Saurabh Chhabra and Ciurea, {Stefan Octavian} and Zachariah DeFilipp and Nosha Farhadfar and Shahinaz Gadalla and Gale, {Robert Peter} and Siddhartha Ganguly and Lohith Gowda and Grunwald, {Michael R.} and Shahrukh Hashmi and Gerhard Hildebrandt and Kanakry, {Christopher G.} and Ankit Kansagra and Farhad Khimani and Maxwell Krem and Hillard Lazarus and Hongtao Liu and Rodrigo Martino and Michelis, {Fotios V.} and Sunita Nathan and Taiga Nishihori and Richard Olsson and Ran Reshef and David Rizzieri and Rowe, {Jacob M.} and Savani, {Bipin N.} and Sachiko Seo and Akshay Sharma and Melhem Solh and Celalettin Ustun and Verdonck, {Leo F.} and Christopher Hourigan and Brenda Sandmaier and Mark Litzow and Partow Kebriaei and Daniel Weisdorf and Yanming Zhang and Tallman, {Martin S.} and Wael Saber",

year = "2022",

month = feb,

day = "8",

doi = "10.1182/bloodadvances.2021004881",

language = "English (US)",

volume = "6",

pages = "828--847",

journal = "Blood advances",

issn = "2473-9529",

publisher = "American Society of Hematology",

number = "3",

}

Menghrajani, K, Gomez-Arteaga, A, Madero-Marroquin, R, Zhang, MJ, Bo-Subait, K, Sanchez, J, Wang, HL, Aljurf, M, Assal, A, Bacher, VU, Badawy, SM, Bejanyan, N, Bhatt, VR, Bredeson, C, Byrne, M, Castillo, P, Cerny, J, Chhabra, S, Ciurea, SO, DeFilipp, Z, Farhadfar, N, Gadalla, S, Gale, RP, Ganguly, S, Gowda, L, Grunwald, MR, Hashmi, S, Hildebrandt, G, Kanakry, CG, Kansagra, A, Khimani, F, Krem, M, Lazarus, H, Liu, H, Martino, R, Michelis, FV, Nathan, S, Nishihori, T, Olsson, R, Reshef, R, Rizzieri, D, Rowe, JM, Savani, BN, Seo, S, Sharma, A, Solh, M, Ustun, C, Verdonck, LF, Hourigan, C, Sandmaier, B, Litzow, M, Kebriaei, P, Weisdorf, D, Zhang, Y, Tallman, MS & Saber, W 2022, 'Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML', Blood Advances, vol. 6, no. 3, pp. 828-847. https://doi.org/10.1182/bloodadvances.2021004881

TY - JOUR

T1 - Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML

AU - Menghrajani, Kamal

AU - Gomez-Arteaga, Alexandra

AU - Madero-Marroquin, Rafael

AU - Zhang, Mei Jie

AU - Bo-Subait, Khalid

AU - Sanchez, Jonathan

AU - Wang, Hai Lin

AU - Aljurf, Mahmoud

AU - Assal, Amer

AU - Bacher, Vera Ulrike

AU - Badawy, Sherif M.

AU - Bejanyan, Nelli

AU - Bhatt, Vijaya Raj

AU - Bredeson, Christopher

AU - Byrne, Michael

AU - Castillo, Paul

AU - Cerny, Jan

AU - Chhabra, Saurabh

AU - Ciurea, Stefan Octavian

AU - DeFilipp, Zachariah

AU - Farhadfar, Nosha

AU - Gadalla, Shahinaz

AU - Gale, Robert Peter

AU - Ganguly, Siddhartha

AU - Gowda, Lohith

AU - Grunwald, Michael R.

AU - Hashmi, Shahrukh

AU - Hildebrandt, Gerhard

AU - Kanakry, Christopher G.

AU - Kansagra, Ankit

AU - Khimani, Farhad

AU - Krem, Maxwell

AU - Lazarus, Hillard

AU - Liu, Hongtao

AU - Martino, Rodrigo

AU - Michelis, Fotios V.

AU - Nathan, Sunita

AU - Nishihori, Taiga

AU - Olsson, Richard

AU - Reshef, Ran

AU - Rizzieri, David

AU - Rowe, Jacob M.

AU - Savani, Bipin N.

AU - Seo, Sachiko

AU - Sharma, Akshay

AU - Solh, Melhem

AU - Ustun, Celalettin

AU - Verdonck, Leo F.

AU - Hourigan, Christopher

AU - Sandmaier, Brenda

AU - Litzow, Mark

AU - Kebriaei, Partow

AU - Weisdorf, Daniel

AU - Zhang, Yanming

AU - Tallman, Martin S.

AU - Saber, Wael

PY - 2022/2/8

Y1 - 2022/2/8

N2 - Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P 5 .01; HR, 1.71; P , .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P 5 .002, and HR, 1.47; P , .001), as was overall survival (HR, 1.32; P , .001, and HR, 1.45; P , .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.

AB - Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P 5 .01; HR, 1.71; P , .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P 5 .002, and HR, 1.47; P , .001), as was overall survival (HR, 1.32; P , .001, and HR, 1.45; P , .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.

UR - http://www.scopus.com/inward/record.url?scp=85124675874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85124675874&partnerID=8YFLogxK

U2 - 10.1182/bloodadvances.2021004881

DO - 10.1182/bloodadvances.2021004881

M3 - Article

C2 - 34551064

AN - SCOPUS:85124675874

SN - 2473-9529

VL - 6

SP - 828

EP - 847

JO - Blood advances

JF - Blood advances

IS - 3

ER -

Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML

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