Measurable residual mutated IDH1 before allogeneic transplant for acute myeloid leukemia

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. Persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoietic cell transplant (alloHCT) associates with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark however remain incompletely defined. We performed testing for residual IDH1 variants (IDH1m) in pre-transplant CR1 blood of 148 adult patients undergoing alloHCT for IDH1-mutated AML at a CIBMTR reporting site between 2013 and 2019. No statistically significant post-transplant differences were observed between those testing IDH1m positive (n = 53, 36%) and negative pre-transplant (overall survival (OS): p = 0.4; relapse: p = 0.5). For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3-ITD, only detection of persistent mutated NPM1 and/or FLT3-ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD for increased post-transplant relapse risk.

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Publication Details

Journal
Bone Marrow Transplantation
Published
2024-11-06
DOI
https://doi.org/10.1038/s41409-024-02447-4
Citations
8
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
3.64

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article

Measurable residual mutated IDH1 before allogeneic transplant for acute myeloid leukemia

Scott L. Zeger, Niveditha Ravindra, Steven M. Devine, Kristin Page et al.
8 citations
Bone Marrow Transplantation
Acute Myeloid Leukemia Research
3.64
article

Measurable residual mutated IDH1 before allogeneic transplant for acute myeloid leukemia

Scott L. Zeger, Niveditha Ravindra, Steven M. Devine, Kristin Page, Antonio Jiménez, Zoë C. Wong, Pranay S. Hegde, Yi‐Bin Chen, Marcos de Lima, Devdeep Mukherjee, Evan Chris Chen, Firas El Chaer, Georgia Andrew, Gege Gui, Laura W. Dillon, Wael Saber, Christopher Simon Hourigan, Stephen R. Spellman, Partow Kebriaei, Sunil Iyer, Mark Robert Litzow, Jeffery J. Auletta, Adam Corner
article en
8 citations

Abstract

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. Persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoietic cell transplant (alloHCT) associates with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark however remain incompletely defined. We performed testing for residual IDH1 variants (IDH1m) in pre-transplant CR1 blood of 148 adult patients undergoing alloHCT for IDH1-mutated AML at a CIBMTR reporting site between 2013 and 2019. No statistically significant post-transplant differences were observed between those testing IDH1m positive (n = 53, 36%) and negative pre-transplant (overall survival (OS): p = 0.4; relapse: p = 0.5). For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3-ITD, only detection of persistent mutated NPM1 and/or FLT3-ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD for increased post-transplant relapse risk.

Bone Marrow TransplantationVol. 60(2)
National Institutes of Health (US), National Marrow Donor Program (US), Bio-Rad (United States) (US), The University of Texas MD Anderson Cancer Center (US), Johns Hopkins University (US), Medical College of Wisconsin (US), Columbia University Irving Medical Center (US), Massachusetts General Hospital (US), Institute of Cancer Research (CA), National Heart, Lung, and Blood Institute (US), Dana-Farber Cancer Institute (US), Mayo Clinic in Arizona (US), Cancer Research Center (US), Biomedical Research Institute (US), Sylvester Comprehensive Cancer Center (US), University of Virginia (US), The Ohio State University (US), Virginia Tech (US)
U.S. Department of Defense, Foundation for the National Institutes of Health, Amgen, AstraZeneca, Gilead Sciences, Jazz Pharmaceuticals, Syndax Pharmaceuticals, National Institutes of Health, Health Resources and Services Administration, Genentech, U.S. Navy, National Heart, Lung, and Blood Institute, Office of Naval Research, National Cancer Institute, National Institute of Allergy and Infectious Diseases
Good health and well-being
Openalex Percentile: Top 6%
Acute Myeloid Leukemia Research
3.64
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