Impact of diagnostic genetics on remission MRD and transplantation outcomes in older patients with AML

作者：H. Moses Murdock, Haesook T. Kim, Nathan Denlinger, Pankit J. Vachhani, Bryan Christopher Hambley, Bryan S. Manning, Shannon H. Gier, Christina Cho, Harrison Kwei Tsai, Shannon R. McCurdy, Vincent T. Ho, John Koreth, Robert J. Soiffer, Jerome Ritz, Martin Carroll, Sumithira Vasu, Miguel‐Angel Perales, Eunice S. Wang, Lukasz P. Gondek, Steven Michael Devine, Edwin Pascal Alyea, Robert Coleman Lindsley, Christopher James Gibson · 发表于：Blood · 年份：2022 · DOI：10.1182/blood.2021014520 · 被引用次数：76 · 研究领域：Acute Myeloid Leukemia Research、Hematopoietic Stem Cell Transplantation、Myeloproliferative Neoplasms: Diagnosis and Treatment

Older patients with acute myeloid leukemia (AML) have high relapse risk and poor survival after allogeneic hematopoietic cell transplantation (HCT). Younger patients may receive myeloablative conditioning to mitigate relapse risk associated with high-risk genetics or measurable residual disease (MRD), but older adults typically receive reduced-intensity conditioning (RIC) to limit toxicity. To identify factors that drive HCT outcomes in older patients, we performed targeted mutational analysis (variant allele fraction ≥2%) on diagnostic samples from 295 patients with AML aged ≥60 years who underwent HCT in first complete remission, 91% of whom received RIC, and targeted duplex sequencing at remission in a subset comprising 192 patients. In a multivariable model for leukemia-free survival (LFS) including baseline genetic and clinical variables, we defined patients with low (3-year LFS, 85%), intermediate (55%), high (35%), and very high (7%) risk. Before HCT, 79.7% of patients had persistent baseline mutations, including 18.3% with only DNMT3A or TET2 (DT) mutations and 61.4% with other mutations (MRD positive). In univariable analysis, MRD positivity was associated with increased relapse and inferior LFS, compared with DT and MRD-negative mutations. However, in a multivariable model accounting for baseline risk, MRD positivity had no independent impact on LFS, most likely because of its significant association with diagnostic genetic characteristics, including MDS-associated ...