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

Media type: E-Article
Title: Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation
Contributor: Kunadt, Desiree; Stasik, Sebastian; Metzeler, Klaus H.; Röllig, Christoph; Schliemann, Christoph; Greif, Philipp A.; Spiekermann, Karsten; Rothenberg-Thurley, Maja; Krug, Utz; Braess, Jan; Krämer, Alwin; Hochhaus, Andreas; Scholl, Sebastian; Hilgendorf, Inken; Brümmendorf, Tim H.; Jost, Edgar; Steffen, Björn; Bug, Gesine; Einsele, Hermann; Görlich, Dennis; Sauerland, Cristina; Schäfer-Eckart, Kerstin; Krause, Stefan W.; Hänel, Mathias; [...]
imprint: Springer Science and Business Media LLC, 2022
Published in: Journal of Hematology & Oncology
Language: English
DOI: 10.1186/s13045-022-01339-8
ISSN: 1756-8722
Origination:
Footnote:
Description: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The role of allogeneic hematopoietic cell transplantation (alloHCT) in acute myeloid leukemia (AML) with mutated<jats:italic>IDH1/2</jats:italic>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<jats:italic>IDH1/2</jats:italic>mutational subgroups (<jats:italic>IDH1</jats:italic>R132C, R132H and <jats:italic>IDH2</jats:italic> R140Q, R172K).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Genomic DNA was extracted from bone marrow or peripheral blood samples at diagnosis and analyzed for<jats:italic>IDH</jats:italic>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Among 3234 patients achieving CR1, 7.8% harbored<jats:italic>IDH1</jats:italic>mutations (36% R132C and 47% R132H) and 10.9% carried<jats:italic>IDH2</jats:italic>mutations (77% R140Q and 19% R172K). 852 patients underwent alloHCT in CR1. Within the alloHCT group, 6.2% had an<jats:italic>IDH1</jats:italic>mutation (43.4% R132C and 41.4% R132H) and 10% were characterized by an<jats:italic>IDH2</jats:italic>mutation (71.8% R140Q and 24.7% R172K). Variants <jats:italic>IDH1</jats:italic> R132C and <jats:italic>IDH2</jats:italic> R172K showed a significant benefit from alloHCT for OS (<jats:italic>p</jats:italic> = .017 and<jats:italic>p</jats:italic> = .049) and RFS (HR = 0.42,<jats:italic>p</jats:italic> = .048 and<jats:italic>p</jats:italic> = .009) compared with chemotherapy only. AlloHCT in <jats:italic>IDH2</jats:italic> R140Q mutated AML resulted in longer RFS (HR = 0.4,<jats:italic>p</jats:italic> = .002).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In this large as-treated analysis, we showed that alloHCT is able to overcome the negative prognostic impact of certain<jats:italic>IDH</jats:italic>mutational subclasses in first-line consolidation treatment and could pending prognostic validation, provide prognostic value for AML risk stratification and therapeutic decision making.</jats:p></jats:sec>
Access State: Open Access

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