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02 July 2024 : Original article  

Clonal Hematopoiesis-Associated Gene Mutations Affect Acute Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation in AML Patients

Xiaoxuan Wei12ABCDEF, Sai Huang1ABF, Zhenyang Gu1ADEF, Jing Liu1ADEF, Meng Li1AF, Xiangshu Jin1AF, Jian Bo1AF, Fei Li1A, Yu Jing1A, Xiaoning Gao1A, Liping Dou1AB, Daihong Liu1A, Chunji Gao1ADEF*

DOI: 10.12659/AOT.943688

Ann Transplant 2024; 29:e943688

Abstract

BACKGROUND: The relationship between clonal hematopoiesis (CH)-associated gene mutations and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been extensively studied since next-generation sequencing (NGS) technology became widely available. However, research has mainly focused on the relationship between donor CH mutations and transplant prognosis, and research into the relationship between CH mutations in the recipient and acute graft-versus-host disease (aGVHD) is lacking.

MATERIAL AND METHODS: We analyzed NGS results and their correlation with aGVHD and prognosis in 196 AML patients undergoing allo-HSCT.

RESULTS: A total of 93 (47.4%) patients had CH mutations. The most frequently mutated genes were DNMT3A (28 of 196; 14.3%), TET2 (22 of 196; 11.2%), IDH1 (15 of 196; 7.7%), IDH2 (14 of 196; 7.1%), and ASXL1 (13 of 196; 6.6%). The incidence of aGVHD was higher in patients older than 45 years old with DTA mutations (DNMT3A, TET2 or ASXL1). DNMT3A mutation but not with TET2 or ASXL1 mutation was an independent risk factor for aGVHD in patients receiving allo-HSCT older than 45 years old. With a median follow-up of 42.7 months, CH mutations were not associated with overall survival and leukemia-free survival.

CONCLUSIONS: DNMT3A mutation, but not TET2 or ASXL1 mutation, was associated with higher incidence of aGVHD.

Keywords: Clonal Hematopoiesis, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute

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Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358