Hong Wang1,2,3, Xue-Qian Li1,2, Tian-Tian Chu1,2, Shi-Yu Han1,2, Jia-Qian Qi1,2,3, Ya-Qiong Tang1,2,3, Hui-Ying Qiu1,2,3,4, Cheng-Cheng Fu1,2,3,4, Xiao-Wen Tang1,2,3,4, Chang-Geng Ruan1,2,3,4, De-Pei Wu5,6,7,8, Yue Han9,10,11,12. 1. Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215000, China. 2. Collaborative Innovation Center of Hematology, Institute of Blood and Marrow Transplantation, Suzhou, China. 3. Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China. 4. State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China. 5. Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215000, China. wudepeisz@163.com. 6. Collaborative Innovation Center of Hematology, Institute of Blood and Marrow Transplantation, Suzhou, China. wudepeisz@163.com. 7. Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China. wudepeisz@163.com. 8. State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China. wudepeisz@163.com. 9. Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215000, China. hanyue@suda.edu.cn. 10. Collaborative Innovation Center of Hematology, Institute of Blood and Marrow Transplantation, Suzhou, China. hanyue@suda.edu.cn. 11. Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China. hanyue@suda.edu.cn. 12. State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China. hanyue@suda.edu.cn.
Abstract
PURPOSE: Genetic changes have prognostic significance in cytogenetically normal acute myeloid leukemia (CN-AML). We set out to evaluate the prognostic of 6 gene mutations in CN-AML. METHODS: We performed a mutational analysis and evaluated prognostic findings of six genes (NPM1, CEBPA, DNMT3A, FLT3-ITD, FLT3-TKD, and C-KIT) in 428 CN-AML patients at our center over 10 years. RESULTS: A total of 282 patients (65.9%) had at least one gene mutation, and the mutation frequencies were as follows: 29.7% (NPM1), 24.1% (CEBPA), 20.1% (FLT3-ITD), 4.0% (FLT3-TKD), 11.9% (DNMT3A), and 4.7% (C-KIT). Multivariate analysis indicated that FLT3-ITDmut and CEBPAwt were independent risk factors correlated with poor overall survival (OS) and disease-free survival (DFS) of CN-AML. Compared with patients who received chemotherapy as consolidation, hematopoietic stem cell transplantation (HSCT) significantly improved OS of CN-AML patients. For standard/high risk patients, HSCT improved both OS and DFS. Combined analysis showed that patients with CEBPAmut/FLT3-ITDwt had the best prognosis, and patients with CEBPAwt/FLT3-ITDmut had the worst OS, with 3-year OS of only 44%. In 212 patients who received HSCT, FLT3-ITD/CEBPA mutations and minimal residual disease (MRD) were correlated with OS and DFS in univariate analysis. CONCLUSIONS: We found that HSCT significantly improves the prognosis of standard/high risk CN-AML patients with superior OS and DFS. Molecular marker analyses, especially combined analysis of the FLT3-ITD and CEBPA status revealed a correlation with the prognosis of CN-AML. For patients who have received HSCT, MRD before transplantation was a strong prognostic marker predicting patient outcome.
PURPOSE: Genetic changes have prognostic significance in cytogenetically normal acute myeloid leukemia (CN-AML). We set out to evaluate the prognostic of 6 gene mutations in CN-AML. METHODS: We performed a mutational analysis and evaluated prognostic findings of six genes (NPM1, CEBPA, DNMT3A, FLT3-ITD, FLT3-TKD, and C-KIT) in 428 CN-AMLpatients at our center over 10 years. RESULTS: A total of 282 patients (65.9%) had at least one gene mutation, and the mutation frequencies were as follows: 29.7% (NPM1), 24.1% (CEBPA), 20.1% (FLT3-ITD), 4.0% (FLT3-TKD), 11.9% (DNMT3A), and 4.7% (C-KIT). Multivariate analysis indicated that FLT3-ITDmut and CEBPAwt were independent risk factors correlated with poor overall survival (OS) and disease-free survival (DFS) of CN-AML. Compared with patients who received chemotherapy as consolidation, hematopoietic stem cell transplantation (HSCT) significantly improved OS of CN-AMLpatients. For standard/high risk patients, HSCT improved both OS and DFS. Combined analysis showed that patients with CEBPAmut/FLT3-ITDwt had the best prognosis, and patients with CEBPAwt/FLT3-ITDmut had the worst OS, with 3-year OS of only 44%. In 212 patients who received HSCT, FLT3-ITD/CEBPA mutations and minimal residual disease (MRD) were correlated with OS and DFS in univariate analysis. CONCLUSIONS: We found that HSCT significantly improves the prognosis of standard/high risk CN-AMLpatients with superior OS and DFS. Molecular marker analyses, especially combined analysis of the FLT3-ITD and CEBPA status revealed a correlation with the prognosis of CN-AML. For patients who have received HSCT, MRD before transplantation was a strong prognostic marker predicting patient outcome.
Authors: K Yamada; S Furusawa; K Saito; K Waga; T Koike; H Arimura; A Aoyagi; H Yamato; H Sakuma; S Tsunogake Journal: Leukemia Date: 1995-01 Impact factor: 11.528