AUTHOR=Wu Li-Xin , Jiang Hao , Chang Ying-Jun , Zhou Ya-Lan , Wang Jing , Wang Zi-Long , Cao Lei-Ming , Li Jin-Lan , Sun Qiu-Yu , Cao Shan-Bo , Lou Feng , Zhou Tao , Liu Li-Xia , Wang Cheng-Cheng , Wang Yu , Jiang Qian , Xu Lan-Ping , Zhang Xiao-Hui , Liu Kai-Yan , Huang Xiao-Jun , Ruan Guo-Rui 

TITLE=Risk Stratification of Cytogenetically Normal Acute Myeloid Leukemia With Biallelic CEBPA Mutations Based on a Multi-Gene Panel and Nomogram Model

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.706935

DOI=10.3389/fonc.2021.706935

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Approximately 30% of Chinese individuals with cytogenetically normal acute myeloid leukemia (CN-AML) have biallelic <italic>CEBPA</italic> (bi<italic>CEBPA</italic>) mutations. The prognosis and optimal therapy for these patients are controversial in clinical practice.</p></sec><sec><title>Methods</title><p>In this study, we performed targeted region sequencing of 236 genes in 158 individuals with this genotype and constructed a nomogram model based on leukemia-free survival (LFS). Patients were randomly assigned to a training cohort (<italic>N </italic>=111) and a validation cohort (<italic>N</italic> =47) at a ratio of 7:3. Risk stratification was performed by the prognostic factors to investigate the risk-adapted post-remission therapy by Kaplan–Meier method.</p></sec><sec><title>Results</title><p>At least 1 mutated gene other than <italic>CEBPA</italic> was identified in patients and mutation number was associated with LFS (61.6% <italic>vs.</italic> 39.0%, <italic>P</italic> =0.033), survival (85.6% <italic>vs.</italic> 62.9%, <italic>P</italic> =0.030) and cumulative incidence of relapse (CIR) (38.4% <italic>vs.</italic> 59.5%, <italic>P</italic> =0.0496). White blood cell count, mutations in <italic>CFS3R</italic>, <italic>KMT2A</italic> and DNA methylation related genes were weighted to construct a nomogram model and differentiate two risk subgroups. Regarding LFS, low-risk patients were superior to the high-risk (89.3% <italic>vs.</italic> 33.8%, <italic>P &lt;</italic>0.001 in training cohort; 87.5% <italic>vs.</italic> 18.2%, <italic>P</italic> =0.009 in validation cohort). Compared with chemotherapy, allogenic hematopoietic stem cell transplantation (allo-HSCT) improved 5-year LFS (89.6% <italic>vs.</italic> 32.6%, <italic>P &lt;</italic>0.001), survival (96.9% <italic>vs.</italic> 63.6%, <italic>P</italic> =0.001) and CIR (7.2% <italic>vs.</italic> 65.8%, <italic>P &lt;</italic>0.001) in high-risk patients but not low-risk patients (LFS, 77.4% <italic>vs.</italic> 88.9%, <italic>P</italic> =0.424; survival, 83.9% <italic>vs.</italic> 95.5%, <italic>P</italic> =0.173; CIR, 11.7% <italic>vs.</italic> 11.1%, <italic>P</italic> =0.901).</p></sec><sec><title>Conclusions</title><p>Our study indicated that bi<italic>CEBPA</italic> mutant-positive CN-AML patients could be further classified into two risk subgroups by four factors and allo-HSCT should be recommended for high-risk patients as post-remission therapy. These data will help physicians refine treatment decision-making in bi<italic>CEBPA</italic> mutant-positive CN-AML patients.</p></sec>