Acute Myeloid Leukemia with Normal Cytogenetics and <i>NPM1</i>-Mutation: Impact of Mutation Topography on Outcomes
Mingyue Zhao,
Mingyue Liao,
Robert Peter Gale,
Meijie Zhang,
Lixin Wu,
Nan Yan,
Lixia Liu,
Jiayue Qin,
Shanbo Cao,
Yingjun Chang,
Qian Jiang,
Lanping Xu,
Xiaohui Zhang,
Xiaojun Huang,
Hao Jiang,
Guorui Ruan
Affiliations
Mingyue Zhao
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Peking University People’s Hospital, Beijing 100044, China
Mingyue Liao
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Peking University People’s Hospital, Beijing 100044, China
Robert Peter Gale
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Peking University People’s Hospital, Beijing 100044, China
Meijie Zhang
Division of Biostatistics, Medical College of Wisconsin, IBMTR/ABMTR, Milwaukee, WI 53226, USA
Lixin Wu
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Peking University People’s Hospital, Beijing 100044, China
Nan Yan
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Peking University People’s Hospital, Beijing 100044, China
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Peking University People’s Hospital, Beijing 100044, China
Qian Jiang
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Peking University People’s Hospital, Beijing 100044, China
Lanping Xu
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Peking University People’s Hospital, Beijing 100044, China
Xiaohui Zhang
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Peking University People’s Hospital, Beijing 100044, China
Xiaojun Huang
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Peking University People’s Hospital, Beijing 100044, China
Hao Jiang
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Peking University People’s Hospital, Beijing 100044, China
Guorui Ruan
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Peking University People’s Hospital, Beijing 100044, China
Background: About half of adults with acute myeloid leukemia with normal cytogenetics (CN-AML) have NPM1 mutations. There is controversy regarding their prognosis and best therapy. Methods: We studied 150 subjects with these features using targeted regional sequencing. Prognostic stratification was carried out based on risk factors, and we assessed the effects of two post-remission strategies with and without transplant across risk cohorts. Results: In multi-variable analyses, a positive MRD test after the second consolidation cycle (HR = 6.00; 95% CI [3.31, 10.85]; p DNMT3A mutations (HR = 3.01 [1.57, 5.78]; p FLT3-ITD mutation with high variant allele frequency (HR = 4.40 [1.89, 10.24]; p DDX11 mutations (HR = 4.38 [2.38, 8.04]; p p 0.001; HR = 2.99 [1.60, 5.62]; p 0.001; HR = 4.20 [1.87, 9.40]; p 0.001; and HR = 4.22, 95% CI [1.99, 8.95], p 0.001). Subjects with ≥1 high-risk co-variate who received a transplant had a lower CIR and better LFS, whereas others did not. Conclusions: We identified co-variates associated with CIR and LFS in subjects of NPM1-mutated CN-AML.
