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

التفاصيل البيبلوغرافية
العنوان: Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation
المؤلفون: 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)
المصدر: Journal of Hematology & Oncology, Vol 15, Iss 1, Pp 1-15 (2022)
بيانات النشر: BMC, 2022.
سنة النشر: 2022
المجموعة: LCC:Diseases of the blood and blood-forming organs
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: Acute myeloid leukemia, IDH mutations, Allogeneic hematopoietic cell transplantation, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1756-8722
Relation: https://doaj.org/toc/1756-8722
DOI: 10.1186/s13045-022-01339-8
URL الوصول: https://doaj.org/article/1665eacc6b1a46028a7f2723eae46d4a
رقم الانضمام: edsdoj.1665eacc6b1a46028a7f2723eae46d4a
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:17568722
DOI:10.1186/s13045-022-01339-8