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

Kunadt D, Stasik S, Metzeler KH, Roellig C, Schliemann C, Greif PA, Spiekermann K, Rothenberg-Thurley M, Krug U, Braess J, Kraemer A, Hochhaus A, Scholl S, Hilgendorf I, Bruemmendorf TH, Jost E, Steffen B, Bug G, Einsele H, Goerlich D, Sauerland C, Schaefer-Eckart K, Krause S, Haenel M, Hanoun M, Kaufmann M, Woermann B, Kramer M, Sockel K, Egger-Heidrich K, Herold T, Ehninger G, Burchert A, Platzbecker U, Berdel WE, Mueller-Tidow C, Hiddemann W, Serve H, Stelljes M, Baldus CD, Neubauer A, Schetelig J, Thiede C, Bornhaeuser M, Middeke JM, Stoelzel F (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 15

Pages Range: 126-

Journal Issue: 1

DOI: 10.1186/s13045-022-01339-8

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.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Ludwig-Maximilians-Universität (LMU) Germany (DE) Universitätsklinikum Münster Germany (DE) Klinikum Leverkusen Germany (DE) Krankenhaus Barmherzige Brüder Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) Universitätsklinikum Jena Germany (DE) Universitätsklinikum Aachen (UKA) Germany (DE) Goethe-Universität Frankfurt am Main Germany (DE) Universitätsklinikum Würzburg Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) Paracelsus Medizinische Privatuniversität, Nürnberg Germany (DE) Klinikum Chemnitz Germany (DE) Universitätsklinikum Essen Germany (DE) Robert-Bosch-Krankenhaus Germany (DE) Philipps-Universität Marburg Germany (DE) Universitätsklinikum Leipzig Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE)

How to cite

APA:

Kunadt, D., Stasik, S., Metzeler, K.H., Roellig, C., Schliemann, C., Greif, P.A.,... Stoelzel, F. (2022). Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation. Journal of Hematology & Oncology, 15(1), 126-. https://doi.org/10.1186/s13045-022-01339-8

MLA:

Kunadt, Desiree, et al. "Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation." Journal of Hematology & Oncology 15.1 (2022): 126-.

BibTeX: Download