Gege Gui, Niveditha Ravindra, Pranay S Hegde, Georgia Andrew, Devdeep Mukherjee, Zoë Wong, Jeffery J Auletta, Firas El Chaer, Evan C Chen, Yi-Bin Chen, Adam Corner, Steven M Devine, Sunil G Iyer, Antonio Martin Jimenez Jimenez, Marcos J G De Lima, Mark R Litzow, Partow Kebriaei, Wael Saber, Stephen R Spellman, Scott L Zeger, Kristin M Page, Laura W Dillon, Christopher S Hourigan
{"title":"急性髓性白血病异基因移植前可测量的残留突变 IDH2。","authors":"Gege Gui, Niveditha Ravindra, Pranay S Hegde, Georgia Andrew, Devdeep Mukherjee, Zoë Wong, Jeffery J Auletta, Firas El Chaer, Evan C Chen, Yi-Bin Chen, Adam Corner, Steven M Devine, Sunil G Iyer, Antonio Martin Jimenez Jimenez, Marcos J G De Lima, Mark R Litzow, Partow Kebriaei, Wael Saber, Stephen R Spellman, Scott L Zeger, Kristin M Page, Laura W Dillon, Christopher S Hourigan","doi":"10.1038/s41409-024-02449-2","DOIUrl":null,"url":null,"abstract":"<p><p>Routine genetic profiling of acute myeloid leukemia (AML) at initial diagnosis has allowed subgroup specific prognostication, drug development, and clinical management strategies. The optimal approach for treatment response assessment for AML subgroups has not yet however been determined. A nationwide cohort of 257 adult patients in first remission (CR1) from AML associated with an IDH2 mutation (IDH2m) undergoing allogeneic transplant during the period 2013-2019 in the United States had rates of relapse and survival three years after transplantation of 24% and 71%, respectively. Pre-transplant clinical flow cytometry assessment was not useful in stratifying patients based on risk of post-transplant relapse or death. DNA-sequencing was performed on CR1 blood collected within 100 days before transplant. Persistent detection of IDH2m was common (51%) and associated with increased relapse and death compared to testing negative. Co-mutation at initial diagnosis with mutated NPM1 and/or FLT3-ITD was common in this cohort (41%) and use of these validated MRD markers provided superior stratification compared to IDH2m testing. Patients testing negative for IDH2m prior to transplant had low relapse-related death, regardless of conditioning intensity. Post-transplant relapse rates for those with persistently detectable IDH2m in pre-transplant remission were lower after the FDA approval of enasidenib in August 2017.</p>","PeriodicalId":9126,"journal":{"name":"Bone Marrow Transplantation","volume":" ","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Measurable residual mutated IDH2 before allogeneic transplant for acute myeloid leukemia.\",\"authors\":\"Gege Gui, Niveditha Ravindra, Pranay S Hegde, Georgia Andrew, Devdeep Mukherjee, Zoë Wong, Jeffery J Auletta, Firas El Chaer, Evan C Chen, Yi-Bin Chen, Adam Corner, Steven M Devine, Sunil G Iyer, Antonio Martin Jimenez Jimenez, Marcos J G De Lima, Mark R Litzow, Partow Kebriaei, Wael Saber, Stephen R Spellman, Scott L Zeger, Kristin M Page, Laura W Dillon, Christopher S Hourigan\",\"doi\":\"10.1038/s41409-024-02449-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Routine genetic profiling of acute myeloid leukemia (AML) at initial diagnosis has allowed subgroup specific prognostication, drug development, and clinical management strategies. The optimal approach for treatment response assessment for AML subgroups has not yet however been determined. A nationwide cohort of 257 adult patients in first remission (CR1) from AML associated with an IDH2 mutation (IDH2m) undergoing allogeneic transplant during the period 2013-2019 in the United States had rates of relapse and survival three years after transplantation of 24% and 71%, respectively. Pre-transplant clinical flow cytometry assessment was not useful in stratifying patients based on risk of post-transplant relapse or death. DNA-sequencing was performed on CR1 blood collected within 100 days before transplant. Persistent detection of IDH2m was common (51%) and associated with increased relapse and death compared to testing negative. Co-mutation at initial diagnosis with mutated NPM1 and/or FLT3-ITD was common in this cohort (41%) and use of these validated MRD markers provided superior stratification compared to IDH2m testing. Patients testing negative for IDH2m prior to transplant had low relapse-related death, regardless of conditioning intensity. Post-transplant relapse rates for those with persistently detectable IDH2m in pre-transplant remission were lower after the FDA approval of enasidenib in August 2017.</p>\",\"PeriodicalId\":9126,\"journal\":{\"name\":\"Bone Marrow Transplantation\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-10-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bone Marrow Transplantation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41409-024-02449-2\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bone Marrow Transplantation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41409-024-02449-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Measurable residual mutated IDH2 before allogeneic transplant for acute myeloid leukemia.
Routine genetic profiling of acute myeloid leukemia (AML) at initial diagnosis has allowed subgroup specific prognostication, drug development, and clinical management strategies. The optimal approach for treatment response assessment for AML subgroups has not yet however been determined. A nationwide cohort of 257 adult patients in first remission (CR1) from AML associated with an IDH2 mutation (IDH2m) undergoing allogeneic transplant during the period 2013-2019 in the United States had rates of relapse and survival three years after transplantation of 24% and 71%, respectively. Pre-transplant clinical flow cytometry assessment was not useful in stratifying patients based on risk of post-transplant relapse or death. DNA-sequencing was performed on CR1 blood collected within 100 days before transplant. Persistent detection of IDH2m was common (51%) and associated with increased relapse and death compared to testing negative. Co-mutation at initial diagnosis with mutated NPM1 and/or FLT3-ITD was common in this cohort (41%) and use of these validated MRD markers provided superior stratification compared to IDH2m testing. Patients testing negative for IDH2m prior to transplant had low relapse-related death, regardless of conditioning intensity. Post-transplant relapse rates for those with persistently detectable IDH2m in pre-transplant remission were lower after the FDA approval of enasidenib in August 2017.
期刊介绍:
Bone Marrow Transplantation publishes high quality, peer reviewed original research that addresses all aspects of basic biology and clinical use of haemopoietic stem cell transplantation.
The broad scope of the journal thus encompasses topics such as stem cell biology, e.g., kinetics and cytokine control, transplantation immunology e.g., HLA and matching techniques, translational research, and clinical results of specific transplant protocols. Bone Marrow Transplantation publishes 24 issues a year.