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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Desiree Kunadt - , Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Sebastian Stasik - , Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Klaus H Metzeler - , Hospital of the Ludwig-Maximilians-University (LMU) Munich (Author)
  • Christoph Röllig - , Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Christoph Schliemann - , Medizinische Klinik (Author)
  • Philipp A Greif - , Hospital of the Ludwig-Maximilians-University (LMU) Munich (Author)
  • Karsten Spiekermann - , Hospital of the Ludwig-Maximilians-University (LMU) Munich (Author)
  • Maja Rothenberg-Thurley - , Hospital of the Ludwig-Maximilians-University (LMU) Munich (Author)
  • Utz Krug - , Medizinische Klinik und Poliklinik III, Bereich Allgemeinmedizin (Author)
  • Jan Braess - , Barmherzige Brüder Hospital Regensburg (Author)
  • Alwin Krämer - , Medizinische Klinik und Poliklinik III, Bereich Allgemeinmedizin (Author)
  • Andreas Hochhaus - , Klinik für Innere Medizin und Kardiologie (Author)
  • Sebastian Scholl - , Klinik für Innere Medizin und Kardiologie (Author)
  • Inken Hilgendorf - , Klinik für Innere Medizin und Kardiologie (Author)
  • Tim H Brümmendorf - , Medizinische Klinik (Author)
  • Edgar Jost - , Medizinische Klinik (Author)
  • Björn Steffen - , Abteilung Hämatologie/Onkologie (Author)
  • Gesine Bug - , Abteilung Hämatologie/Onkologie (Author)
  • Hermann Einsele - , Medizinische Klinik und Poliklinik III, Bereich Allgemeinmedizin (Author)
  • Dennis Görlich - , Institut für Biometrie und Klinische Forschung (Author)
  • Cristina Sauerland - , Institut für Biometrie und Klinische Forschung (Author)
  • Kerstin Schäfer-Eckart - , Klinikum Nurnberg (Author)
  • Stefan W Krause - , State Vocational Colleges at the University Hospital Erlangen (Author)
  • Mathias Hänel - , Medizinische Klinik und Poliklinik III, Bereich Allgemeinmedizin (Author)
  • Maher Hanoun - , Klinik für Hämatologie (Author)
  • Martin Kaufmann - , Abteilung für Hämatologie (Author)
  • Bernhard Wörmann - , Abteilung für Hämatologie (Author)
  • Michael Kramer - , Medizinische Klinik und Poliklinik III, Bereich Allgemeinmedizin (Author)
  • Katja Sockel - , Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Katharina Egger-Heidrich - , Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Tobias Herold - , Hospital of the Ludwig-Maximilians-University (LMU) Munich (Author)
  • Gerhard Ehninger - , Medizinische Klinik und Poliklinik III, Bereich Allgemeinmedizin (Author)
  • Andreas Burchert - , Klinik für Innere Medizin und Kardiologie (Author)
  • Uwe Platzbecker - , University Hospital Leipzig (Author)
  • Wolfgang E Berdel - , Medizinische Klinik (Author)
  • Carsten Müller-Tidow - , Medizinische Klinik und Poliklinik III, Bereich Allgemeinmedizin (Author)
  • Wolfgang Hiddemann - , Hospital of the Ludwig-Maximilians-University (LMU) Munich (Author)
  • Hubert Serve - , Abteilung Hämatologie/Onkologie (Author)
  • Matthias Stelljes - , Medizinische Klinik (Author)
  • Claudia D Baldus - , Klinik für Innere Medizin und Kardiologie (Author)
  • Andreas Neubauer - , Klinik für Innere Medizin und Kardiologie (Author)
  • Johannes Schetelig - , Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden, DKMS Clinical Trials Unit (Author)
  • Christian Thiede - , Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Martin Bornhäuser - , Department of internal Medicine I, University Cancer Centre, National Center for Tumor Diseases (Partners: UKD, MFD, HZDR, DKFZ), German Cancer Consortium (Partner: DKTK, DKFZ), University Hospital Carl Gustav Carus Dresden, German Cancer Consortium (DKTK) Partner Site Dresden, National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Jan M Middeke - , Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Friedrich Stölzel - , Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)

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.

Details

Original languageEnglish
Article number126
JournalJournal of hematology & oncology
Volume15
Issue number1
Publication statusPublished - 5 Sept 2022
Peer-reviewedYes

External IDs

PubMedCentral PMC9442956
Scopus 85137221676

Keywords

Keywords

  • Hematopoietic Stem Cell Transplantation, Humans, Isocitrate Dehydrogenase/genetics, Leukemia, Myeloid, Acute/genetics, Mutation, Nucleophosmin, Prognosis

Library keywords