Sankalp Arora MD, Wei-Ying Jen MD, Musa Yilmaz MD, Indraneel Deshmukh MD, Jayastu Senapati MD, Sanam Loghavi MD, Ghayas C. Issa MD, Nicholas J. Short MD, Tapan M. Kadia MD, Courtney D. DiNardo MD, Gautam Borthakur MD, Joseph Jabbour, Naveen Pemmaraju MD, Michael Andreeff MD, PhD, Koichi Takahashi MD, PhD, Kapil Bhalla MD, Uday Popat MD, Elizabeth J. Shpall MD, Betul Oran MD, Hussein A. Abbas MD, PhD, Guillermo Garcia-Manero MD, Farhad Ravandi MD, Hagop Kantarjian MD, Naval Daver MD
{"title":"flt3 -酪氨酸激酶结构域突变的新诊断急性髓系白血病患者的预后：NPM1共突变的预后意义","authors":"Sankalp Arora MD, Wei-Ying Jen MD, Musa Yilmaz MD, Indraneel Deshmukh MD, Jayastu Senapati MD, Sanam Loghavi MD, Ghayas C. Issa MD, Nicholas J. Short MD, Tapan M. Kadia MD, Courtney D. DiNardo MD, Gautam Borthakur MD, Joseph Jabbour, Naveen Pemmaraju MD, Michael Andreeff MD, PhD, Koichi Takahashi MD, PhD, Kapil Bhalla MD, Uday Popat MD, Elizabeth J. Shpall MD, Betul Oran MD, Hussein A. Abbas MD, PhD, Guillermo Garcia-Manero MD, Farhad Ravandi MD, Hagop Kantarjian MD, Naval Daver MD","doi":"10.1002/cncr.70032","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>The prognostic impact of Fms-like tyrosine kinase 3 (<i>FLT3</i>)-tyrosine kinase domain (TKD) mutation in patients with acute myeloid leukemia (AML) is not well defined. The authors described outcomes of one of the largest cohorts of patients with <i>FLT3</i>-TKD mutated (<i>FLT3</i>-TKD<sup>mut</sup>) AML to date.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This retrospective study included patients with newly diagnosed AML who received frontline treatment at The University of Texas MD Anderson Cancer Center from January 2012 to March 2024 divided into two cohorts: <i>FLT3</i>-TKD<sup>mut</sup> AML and nucleophosmin-mutated (<i>NPM1</i><sup>mut</sup>)/<i>FLT3</i>-TKD wild-type (<i>FLT3</i>-TKD<sup>wt</sup>) AML. Patients with <i>FLT3</i> internal tandem duplication mutations were excluded.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>In total, 2922 patients were screened, and 250 met inclusion criteria, including 124 patients with <i>FLT3</i>-TKD<sup>mut</sup> AML and 126 patients with <i>NPM1</i><sup>mut</sup>/<i>FLT3</i>-TKD<sup>wt</sup> AML. In the <i>FLT3</i>-TKD<sup>mut</sup> cohort (<i>n</i> = 124), intensive chemotherapy was received by 54 patients (44%), with a composite complete remission in 81% and a 3-year overall survival (OS) rate of 56%. An <i>NPM1</i> mutation was noted in 24 patients (44%) who had improved OS (3-year OS, 74% vs. 40%; <i>p</i> = .03). Allogeneic stem cell transplantation improved OS in patients who had <i>NPM1</i><sup>wt</sup> AML (3-year OS, 89% vs. 30%; <i>p</i> = .02) but not in those who had an <i>NPM1</i> mutation. Lower intensity therapy was received by 70 patients (56%), with a composite complete remission in 63% and a 3-year OS rate of 23%. An <i>NPM1</i> mutation was noted in 31 patients (44%) who had improved OS (3-year OS, 32% vs. 16%; <i>p</i> = .04). Allogeneic stem cell transplantation led to a trend toward improved OS in patients who had <i>NPM1</i><sup>wt</sup> AML (3-year OS, 75% vs. 27%; <i>p</i> = .1) but not in those who had <i>NPM1</i><sup>mut</sup> AML. In the <i>NPM1</i><sup>mut</sup>/<i>FLT3</i>-TKD<sup>wt</sup> cohort (<i>n</i> = 126), intensive chemotherapy was received by 46 patients (37%), and lower intensity therapy was received by 80 patients (63%). Compared with the <i>NPM1</i><sup>mut</sup>/<i>FLT3</i>-TKD<sup>mut</sup> cohort, no difference in OS was noted between patients who received intensive chemotherapy and those who received lower intensity therapy.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p><i>FLT3-</i>TKD<sup>mut</sup> AML commonly harbors <i>NPM1</i> co-mutation, which has key prognostic implications. Lack of <i>NPM1</i> co-mutation portends a poor prognosis, and allogenic stem cell transplantation should be strongly considered for patients in first remission.</p>\n </section>\n </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 16","pages":""},"PeriodicalIF":5.1000,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335293/pdf/","citationCount":"0","resultStr":"{\"title\":\"Outcomes of patients with newly diagnosed acute myeloid leukemia with FLT3-tyrosine kinase domain mutations: Prognostic implications of NPM1 co-mutation\",\"authors\":\"Sankalp Arora MD, Wei-Ying Jen MD, Musa Yilmaz MD, Indraneel Deshmukh MD, Jayastu Senapati MD, Sanam Loghavi MD, Ghayas C. Issa MD, Nicholas J. Short MD, Tapan M. Kadia MD, Courtney D. DiNardo MD, Gautam Borthakur MD, Joseph Jabbour, Naveen Pemmaraju MD, Michael Andreeff MD, PhD, Koichi Takahashi MD, PhD, Kapil Bhalla MD, Uday Popat MD, Elizabeth J. Shpall MD, Betul Oran MD, Hussein A. Abbas MD, PhD, Guillermo Garcia-Manero MD, Farhad Ravandi MD, Hagop Kantarjian MD, Naval Daver MD\",\"doi\":\"10.1002/cncr.70032\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>The prognostic impact of Fms-like tyrosine kinase 3 (<i>FLT3</i>)-tyrosine kinase domain (TKD) mutation in patients with acute myeloid leukemia (AML) is not well defined. The authors described outcomes of one of the largest cohorts of patients with <i>FLT3</i>-TKD mutated (<i>FLT3</i>-TKD<sup>mut</sup>) AML to date.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>This retrospective study included patients with newly diagnosed AML who received frontline treatment at The University of Texas MD Anderson Cancer Center from January 2012 to March 2024 divided into two cohorts: <i>FLT3</i>-TKD<sup>mut</sup> AML and nucleophosmin-mutated (<i>NPM1</i><sup>mut</sup>)/<i>FLT3</i>-TKD wild-type (<i>FLT3</i>-TKD<sup>wt</sup>) AML. Patients with <i>FLT3</i> internal tandem duplication mutations were excluded.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>In total, 2922 patients were screened, and 250 met inclusion criteria, including 124 patients with <i>FLT3</i>-TKD<sup>mut</sup> AML and 126 patients with <i>NPM1</i><sup>mut</sup>/<i>FLT3</i>-TKD<sup>wt</sup> AML. In the <i>FLT3</i>-TKD<sup>mut</sup> cohort (<i>n</i> = 124), intensive chemotherapy was received by 54 patients (44%), with a composite complete remission in 81% and a 3-year overall survival (OS) rate of 56%. An <i>NPM1</i> mutation was noted in 24 patients (44%) who had improved OS (3-year OS, 74% vs. 40%; <i>p</i> = .03). Allogeneic stem cell transplantation improved OS in patients who had <i>NPM1</i><sup>wt</sup> AML (3-year OS, 89% vs. 30%; <i>p</i> = .02) but not in those who had an <i>NPM1</i> mutation. Lower intensity therapy was received by 70 patients (56%), with a composite complete remission in 63% and a 3-year OS rate of 23%. An <i>NPM1</i> mutation was noted in 31 patients (44%) who had improved OS (3-year OS, 32% vs. 16%; <i>p</i> = .04). Allogeneic stem cell transplantation led to a trend toward improved OS in patients who had <i>NPM1</i><sup>wt</sup> AML (3-year OS, 75% vs. 27%; <i>p</i> = .1) but not in those who had <i>NPM1</i><sup>mut</sup> AML. In the <i>NPM1</i><sup>mut</sup>/<i>FLT3</i>-TKD<sup>wt</sup> cohort (<i>n</i> = 126), intensive chemotherapy was received by 46 patients (37%), and lower intensity therapy was received by 80 patients (63%). Compared with the <i>NPM1</i><sup>mut</sup>/<i>FLT3</i>-TKD<sup>mut</sup> cohort, no difference in OS was noted between patients who received intensive chemotherapy and those who received lower intensity therapy.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p><i>FLT3-</i>TKD<sup>mut</sup> AML commonly harbors <i>NPM1</i> co-mutation, which has key prognostic implications. Lack of <i>NPM1</i> co-mutation portends a poor prognosis, and allogenic stem cell transplantation should be strongly considered for patients in first remission.</p>\\n </section>\\n </div>\",\"PeriodicalId\":138,\"journal\":{\"name\":\"Cancer\",\"volume\":\"131 16\",\"pages\":\"\"},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2025-08-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335293/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.70032\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer","FirstCategoryId":"3","ListUrlMain":"https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.70032","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Outcomes of patients with newly diagnosed acute myeloid leukemia with FLT3-tyrosine kinase domain mutations: Prognostic implications of NPM1 co-mutation
Background
The prognostic impact of Fms-like tyrosine kinase 3 (FLT3)-tyrosine kinase domain (TKD) mutation in patients with acute myeloid leukemia (AML) is not well defined. The authors described outcomes of one of the largest cohorts of patients with FLT3-TKD mutated (FLT3-TKDmut) AML to date.
Methods
This retrospective study included patients with newly diagnosed AML who received frontline treatment at The University of Texas MD Anderson Cancer Center from January 2012 to March 2024 divided into two cohorts: FLT3-TKDmut AML and nucleophosmin-mutated (NPM1mut)/FLT3-TKD wild-type (FLT3-TKDwt) AML. Patients with FLT3 internal tandem duplication mutations were excluded.
Results
In total, 2922 patients were screened, and 250 met inclusion criteria, including 124 patients with FLT3-TKDmut AML and 126 patients with NPM1mut/FLT3-TKDwt AML. In the FLT3-TKDmut cohort (n = 124), intensive chemotherapy was received by 54 patients (44%), with a composite complete remission in 81% and a 3-year overall survival (OS) rate of 56%. An NPM1 mutation was noted in 24 patients (44%) who had improved OS (3-year OS, 74% vs. 40%; p = .03). Allogeneic stem cell transplantation improved OS in patients who had NPM1wt AML (3-year OS, 89% vs. 30%; p = .02) but not in those who had an NPM1 mutation. Lower intensity therapy was received by 70 patients (56%), with a composite complete remission in 63% and a 3-year OS rate of 23%. An NPM1 mutation was noted in 31 patients (44%) who had improved OS (3-year OS, 32% vs. 16%; p = .04). Allogeneic stem cell transplantation led to a trend toward improved OS in patients who had NPM1wt AML (3-year OS, 75% vs. 27%; p = .1) but not in those who had NPM1mut AML. In the NPM1mut/FLT3-TKDwt cohort (n = 126), intensive chemotherapy was received by 46 patients (37%), and lower intensity therapy was received by 80 patients (63%). Compared with the NPM1mut/FLT3-TKDmut cohort, no difference in OS was noted between patients who received intensive chemotherapy and those who received lower intensity therapy.
Conclusions
FLT3-TKDmut AML commonly harbors NPM1 co-mutation, which has key prognostic implications. Lack of NPM1 co-mutation portends a poor prognosis, and allogenic stem cell transplantation should be strongly considered for patients in first remission.
期刊介绍：
The CANCER site is a full-text, electronic implementation of CANCER, an Interdisciplinary International Journal of the American Cancer Society, and CANCER CYTOPATHOLOGY, a Journal of the American Cancer Society.
CANCER publishes interdisciplinary oncologic information according to, but not limited to, the following disease sites and disciplines: blood/bone marrow; breast disease; endocrine disorders; epidemiology; gastrointestinal tract; genitourinary disease; gynecologic oncology; head and neck disease; hepatobiliary tract; integrated medicine; lung disease; medical oncology; neuro-oncology; pathology radiation oncology; translational research
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
