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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2022

Open Access 01-12-2022 | Acute Myeloid Leukemia | Research

Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation

Authors: Desiree Kunadt, Sebastian Stasik, Klaus H. Metzeler, Christoph Röllig, Christoph Schliemann, Philipp A. Greif, Karsten Spiekermann, Maja Rothenberg-Thurley, Utz Krug, Jan Braess, Alwin Krämer, Andreas Hochhaus, Sebastian Scholl, Inken Hilgendorf, Tim H. Brümmendorf, Edgar Jost, Björn Steffen, Gesine Bug, Hermann Einsele, Dennis Görlich, Cristina Sauerland, Kerstin Schäfer-Eckart, Stefan W. Krause, Mathias Hänel, Maher Hanoun, Martin Kaufmann, Bernhard Wörmann, Michael Kramer, Katja Sockel, Katharina Egger-Heidrich, Tobias Herold, Gerhard Ehninger, Andreas Burchert, Uwe Platzbecker, Wolfgang E. Berdel, Carsten Müller-Tidow, Wolfgang Hiddemann, Hubert Serve, Matthias Stelljes, Claudia D. Baldus, Andreas Neubauer, Johannes Schetelig, Christian Thiede, Martin Bornhäuser, Jan M. Middeke, Friedrich Stölzel, the A. M. L. Cooperative Group (AMLCG), Study Alliance Leukemia (SAL)

Published in: Journal of Hematology & Oncology | Issue 1/2022

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Abstract

Background

The role of allogeneic hematopoietic cell transplantation (alloHCT) in acute myeloid leukemia (AML) with mutated IDH1/2 has not been defined. Therefore, we analyzed a large cohort of 3234 AML patients in first complete remission (CR1) undergoing alloHCT or conventional chemo-consolidation and investigated outcome in respect to IDH1/2 mutational subgroups (IDH1 R132C, R132H and IDH2 R140Q, R172K).

Methods

Genomic DNA was extracted from bone marrow or peripheral blood samples at diagnosis and analyzed for IDH mutations with denaturing high-performance liquid chromatography, Sanger sequencing and targeted myeloid panel next-generation sequencing, respectively. Statistical as-treated analyses were performed using R and standard statistical methods (Kruskal–Wallis test for continuous variables, Chi-square test for categorical variables, Cox regression for univariate and multivariable models), incorporating alloHCT as a time-dependent covariate.

Results

Among 3234 patients achieving CR1, 7.8% harbored IDH1 mutations (36% R132C and 47% R132H) and 10.9% carried IDH2 mutations (77% R140Q and 19% R172K). 852 patients underwent alloHCT in CR1. Within the alloHCT group, 6.2% had an IDH1 mutation (43.4% R132C and 41.4% R132H) and 10% were characterized by an IDH2 mutation (71.8% R140Q and 24.7% R172K). Variants IDH1 R132C and IDH2 R172K showed a significant benefit from alloHCT for OS (p = .017 and p = .049) and RFS (HR = 0.42, p = .048 and p = .009) compared with chemotherapy only. AlloHCT in IDH2 R140Q mutated AML resulted in longer RFS (HR = 0.4, p = .002).

Conclusion

In this large as-treated analysis, we showed that alloHCT is able to overcome the negative prognostic impact of certain IDH mutational subclasses in first-line consolidation treatment and could pending prognostic validation, provide prognostic value for AML risk stratification and therapeutic decision making.
Appendix
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Metadata
Title
Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation
Authors
Desiree Kunadt
Sebastian Stasik
Klaus H. Metzeler
Christoph Röllig
Christoph Schliemann
Philipp A. Greif
Karsten Spiekermann
Maja Rothenberg-Thurley
Utz Krug
Jan Braess
Alwin Krämer
Andreas Hochhaus
Sebastian Scholl
Inken Hilgendorf
Tim H. Brümmendorf
Edgar Jost
Björn Steffen
Gesine Bug
Hermann Einsele
Dennis Görlich
Cristina Sauerland
Kerstin Schäfer-Eckart
Stefan W. Krause
Mathias Hänel
Maher Hanoun
Martin Kaufmann
Bernhard Wörmann
Michael Kramer
Katja Sockel
Katharina Egger-Heidrich
Tobias Herold
Gerhard Ehninger
Andreas Burchert
Uwe Platzbecker
Wolfgang E. Berdel
Carsten Müller-Tidow
Wolfgang Hiddemann
Hubert Serve
Matthias Stelljes
Claudia D. Baldus
Andreas Neubauer
Johannes Schetelig
Christian Thiede
Martin Bornhäuser
Jan M. Middeke
Friedrich Stölzel
the A. M. L. Cooperative Group (AMLCG), Study Alliance Leukemia (SAL)
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2022
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-022-01339-8

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