Helena Bresser, Claudia Schmoor, Olga Grishina, Dietmar Pfeifer, Johanna Thomas, Usama-Ur Rehman, Martina Crysandt, Edgar Jost, Felicitas Thol, Michael Heuser, Katharina S Götze, Richard F Schlenk, Helmut R Salih, Marcus M Schittenhelm, Gerhard Heil, Carsten Schwaenen, Carsten Müller-Tidow, Wolfram Brugger, Andrea Kündgen, Maike de Wit, Aristoteles Giagounidis, Sebastian Scholl, Andreas Neubauer, Jürgen Krauter, Gesine Bug, Annette M May, Ralph Wäsch, Justus Duyster, Konstanze Döhner, Arnold Ganser, Hartmut Döhner, Björn Hackanson, Heiko Becker, Michael Lübbert
{"title":"在地西他滨基础上加用全反式维甲酸或丙戊酸时TP53突变状态对老年急性髓细胞白血病患者的影响","authors":"Helena Bresser, Claudia Schmoor, Olga Grishina, Dietmar Pfeifer, Johanna Thomas, Usama-Ur Rehman, Martina Crysandt, Edgar Jost, Felicitas Thol, Michael Heuser, Katharina S Götze, Richard F Schlenk, Helmut R Salih, Marcus M Schittenhelm, Gerhard Heil, Carsten Schwaenen, Carsten Müller-Tidow, Wolfram Brugger, Andrea Kündgen, Maike de Wit, Aristoteles Giagounidis, Sebastian Scholl, Andreas Neubauer, Jürgen Krauter, Gesine Bug, Annette M May, Ralph Wäsch, Justus Duyster, Konstanze Döhner, Arnold Ganser, Hartmut Döhner, Björn Hackanson, Heiko Becker, Michael Lübbert","doi":"10.1111/ejh.14304","DOIUrl":null,"url":null,"abstract":"<p><p>In a randomized phase II trial (AMLSG 14-09, NCT00867672) of elderly, newly diagnosed AML patients, ATRA combined with decitabine (DEC) significantly improved the overall response rate (ORR) and survival also in patients with adverse-risk genetics, without adding toxicity. We performed a post hoc analysis to determine the predictive impact of TP53 status. Despite a nominally higher ORR, the clinically meaningful survival benefit when adding ATRA to DEC was diminished, but not completely negated, in TP53-mutated patients. Indeed, 2 out of 14 TP53-mutated patients (14%) randomized to a DEC + ATRA-containing regimen lived for > 36 months. Further studies of ATRA combined with hypomethylating agents appear warranted in non-M3 AML patients ineligible for HMA/venetoclax therapy. Trial Registration: ClinicalTrials.gov identifier: NCT00867672.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of TP53 Mutation Status in Elderly AML Patients When Adding All-Trans Retinoic Acid or Valproic Acid to Decitabine.\",\"authors\":\"Helena Bresser, Claudia Schmoor, Olga Grishina, Dietmar Pfeifer, Johanna Thomas, Usama-Ur Rehman, Martina Crysandt, Edgar Jost, Felicitas Thol, Michael Heuser, Katharina S Götze, Richard F Schlenk, Helmut R Salih, Marcus M Schittenhelm, Gerhard Heil, Carsten Schwaenen, Carsten Müller-Tidow, Wolfram Brugger, Andrea Kündgen, Maike de Wit, Aristoteles Giagounidis, Sebastian Scholl, Andreas Neubauer, Jürgen Krauter, Gesine Bug, Annette M May, Ralph Wäsch, Justus Duyster, Konstanze Döhner, Arnold Ganser, Hartmut Döhner, Björn Hackanson, Heiko Becker, Michael Lübbert\",\"doi\":\"10.1111/ejh.14304\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In a randomized phase II trial (AMLSG 14-09, NCT00867672) of elderly, newly diagnosed AML patients, ATRA combined with decitabine (DEC) significantly improved the overall response rate (ORR) and survival also in patients with adverse-risk genetics, without adding toxicity. We performed a post hoc analysis to determine the predictive impact of TP53 status. Despite a nominally higher ORR, the clinically meaningful survival benefit when adding ATRA to DEC was diminished, but not completely negated, in TP53-mutated patients. Indeed, 2 out of 14 TP53-mutated patients (14%) randomized to a DEC + ATRA-containing regimen lived for > 36 months. Further studies of ATRA combined with hypomethylating agents appear warranted in non-M3 AML patients ineligible for HMA/venetoclax therapy. Trial Registration: ClinicalTrials.gov identifier: NCT00867672.</p>\",\"PeriodicalId\":11955,\"journal\":{\"name\":\"European Journal of Haematology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-10-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Haematology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/ejh.14304\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Haematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/ejh.14304","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Impact of TP53 Mutation Status in Elderly AML Patients When Adding All-Trans Retinoic Acid or Valproic Acid to Decitabine.
In a randomized phase II trial (AMLSG 14-09, NCT00867672) of elderly, newly diagnosed AML patients, ATRA combined with decitabine (DEC) significantly improved the overall response rate (ORR) and survival also in patients with adverse-risk genetics, without adding toxicity. We performed a post hoc analysis to determine the predictive impact of TP53 status. Despite a nominally higher ORR, the clinically meaningful survival benefit when adding ATRA to DEC was diminished, but not completely negated, in TP53-mutated patients. Indeed, 2 out of 14 TP53-mutated patients (14%) randomized to a DEC + ATRA-containing regimen lived for > 36 months. Further studies of ATRA combined with hypomethylating agents appear warranted in non-M3 AML patients ineligible for HMA/venetoclax therapy. Trial Registration: ClinicalTrials.gov identifier: NCT00867672.
期刊介绍：
European Journal of Haematology is an international journal for communication of basic and clinical research in haematology. The journal welcomes manuscripts on molecular, cellular and clinical research on diseases of the blood, vascular and lymphatic tissue, and on basic molecular and cellular research related to normal development and function of the blood, vascular and lymphatic tissue. The journal also welcomes reviews on clinical haematology and basic research, case reports, and clinical pictures.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
