Patients with AML and an IDH2-R172 mutation exhibit a unique initial response to intensive chemotherapy induction

Abstract: The utility of a midcycle bone marrow biopsy (BMB) for early assessment of response in patients with acute myeloid leukemia (AML) after intensive chemotherapy (IC) induction is contested. Even when challenged, there is little consideration as to the possibility of different response dynami...

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Main Authors: Meira Yisraeli Salman, Alexander R. Terry, Andriy Derkach, David Nemirovsky, Kuo-Kai Chin, Yannis K. Valtis, Leora Boussi, Theresa Spivey, Wenbin Xiao, Christopher Famulare, Jenna Ciervo, Jacob M. Rowe, Martin S. Tallman, Eytan M. Stein
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Blood Advances
Online Access:http://www.sciencedirect.com/science/article/pii/S2473952925002071
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author Meira Yisraeli Salman
Alexander R. Terry
Andriy Derkach
David Nemirovsky
Kuo-Kai Chin
Yannis K. Valtis
Leora Boussi
Theresa Spivey
Wenbin Xiao
Christopher Famulare
Jenna Ciervo
Jacob M. Rowe
Martin S. Tallman
Eytan M. Stein
author_facet Meira Yisraeli Salman
Alexander R. Terry
Andriy Derkach
David Nemirovsky
Kuo-Kai Chin
Yannis K. Valtis
Leora Boussi
Theresa Spivey
Wenbin Xiao
Christopher Famulare
Jenna Ciervo
Jacob M. Rowe
Martin S. Tallman
Eytan M. Stein
author_sort Meira Yisraeli Salman
collection DOAJ
description Abstract: The utility of a midcycle bone marrow biopsy (BMB) for early assessment of response in patients with acute myeloid leukemia (AML) after intensive chemotherapy (IC) induction is contested. Even when challenged, there is little consideration as to the possibility of different response dynamics among genetically defined subgroups. Clinical observations led to the hypothesis that patients with AML and mutations in IDH2-R172 (R172-m) exhibit particularly slow blast reduction after IC induction. The purpose of this study was to analyze response kinetics of patients with R172-m to IC and compare the dynamics to patients with AML and IDH2-R140 mutations (R140-m). A retrospective single-center analysis was conducted among patients with newly diagnosed IDH2-mutated AML who received IC induction. Dynamics of blast reduction were compared and correlated with outcomes. A total of 52 patients were identified; 33 with R140-m and 19 with R172-m. Patients with R172-m had significantly higher midcycle BMB median blast count (70% vs 5%; P < .001), and their BMBs were slightly more cellular (P = .045). Among the R140-m, 58% had ≤5% blasts vs 0 of the R172-m. Furthermore, it took significantly longer for patients with R172-m to achieve blast clearance (≤5% blasts in BMB) compared to those with R140-m (P = .017). However, there was no difference in overall survival between the 2 groups, and outcomes were similar and favorable. This type of slow blast reduction has only previously been described in patients with acute promyelocytic leukemia. These findings suggest judicial application of reinduction strategies in this subgroup and warrant further investigation.
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spelling doaj-art-77023079d6b440e8938befe3a3da3b1f2025-08-20T03:27:44ZengElsevierBlood Advances2473-95292025-07-019133213322210.1182/bloodadvances.2024015324Patients with AML and an IDH2-R172 mutation exhibit a unique initial response to intensive chemotherapy inductionMeira Yisraeli Salman0Alexander R. Terry1Andriy Derkach2David Nemirovsky3Kuo-Kai Chin4Yannis K. Valtis5Leora Boussi6Theresa Spivey7Wenbin Xiao8Christopher Famulare9Jenna Ciervo10Jacob M. Rowe11Martin S. Tallman12Eytan M. Stein13Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Hematology, Shaare Zedek Medical Center, Jerusalem, IsraelLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, NYLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, NYLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, NYLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, NYLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, NYLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, NYLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, NYLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, NYLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, NYLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, NYDepartment of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel; Department of Hematology and BMT, Rambam Health Care Campus and Technion, Israel Institute of Technology, Haifa, IsraelLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, NYLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY; Correspondence: Eytan M. Stein, Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 530 E 74th St, New York, NY 10021;Abstract: The utility of a midcycle bone marrow biopsy (BMB) for early assessment of response in patients with acute myeloid leukemia (AML) after intensive chemotherapy (IC) induction is contested. Even when challenged, there is little consideration as to the possibility of different response dynamics among genetically defined subgroups. Clinical observations led to the hypothesis that patients with AML and mutations in IDH2-R172 (R172-m) exhibit particularly slow blast reduction after IC induction. The purpose of this study was to analyze response kinetics of patients with R172-m to IC and compare the dynamics to patients with AML and IDH2-R140 mutations (R140-m). A retrospective single-center analysis was conducted among patients with newly diagnosed IDH2-mutated AML who received IC induction. Dynamics of blast reduction were compared and correlated with outcomes. A total of 52 patients were identified; 33 with R140-m and 19 with R172-m. Patients with R172-m had significantly higher midcycle BMB median blast count (70% vs 5%; P < .001), and their BMBs were slightly more cellular (P = .045). Among the R140-m, 58% had ≤5% blasts vs 0 of the R172-m. Furthermore, it took significantly longer for patients with R172-m to achieve blast clearance (≤5% blasts in BMB) compared to those with R140-m (P = .017). However, there was no difference in overall survival between the 2 groups, and outcomes were similar and favorable. This type of slow blast reduction has only previously been described in patients with acute promyelocytic leukemia. These findings suggest judicial application of reinduction strategies in this subgroup and warrant further investigation.http://www.sciencedirect.com/science/article/pii/S2473952925002071
spellingShingle Meira Yisraeli Salman
Alexander R. Terry
Andriy Derkach
David Nemirovsky
Kuo-Kai Chin
Yannis K. Valtis
Leora Boussi
Theresa Spivey
Wenbin Xiao
Christopher Famulare
Jenna Ciervo
Jacob M. Rowe
Martin S. Tallman
Eytan M. Stein
Patients with AML and an IDH2-R172 mutation exhibit a unique initial response to intensive chemotherapy induction
Blood Advances
title Patients with AML and an IDH2-R172 mutation exhibit a unique initial response to intensive chemotherapy induction
title_full Patients with AML and an IDH2-R172 mutation exhibit a unique initial response to intensive chemotherapy induction
title_fullStr Patients with AML and an IDH2-R172 mutation exhibit a unique initial response to intensive chemotherapy induction
title_full_unstemmed Patients with AML and an IDH2-R172 mutation exhibit a unique initial response to intensive chemotherapy induction
title_short Patients with AML and an IDH2-R172 mutation exhibit a unique initial response to intensive chemotherapy induction
title_sort patients with aml and an idh2 r172 mutation exhibit a unique initial response to intensive chemotherapy induction
url http://www.sciencedirect.com/science/article/pii/S2473952925002071
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