{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:13:58Z","timestamp":1784553238463,"version":"3.55.0"},"reference-count":19,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"6","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2025,2,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>To evaluate the survival benefit of chemotherapy intensification in older patients with AML who have not achieved a measurable residual disease (MRD)\u2013negative remission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Five hundred twenty-three patients with AML (median age, 67 years; range, 51-79) without a flow cytometric MRD-negative remission response after a first course of daunorubicin and AraC (DA; including 165 not in remission) were randomly assigned between up to two further courses of DA or intensified chemotherapy\u2014either fludarabine, cytarabine, granulocyte colony-stimulating factor and idarubicin (FLAG-Ida) or DA with cladribine (DAC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Overall survival (OS) was not improved in the intensification arms (DAC\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      DA: hazard ratio [HR], 0.74 [95% CI, 0.55 to 1.01];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .054; FLAG-Ida\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      DA: HR, 0.86 [95% CI, 0.66 to 1.12];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .270); OS at 3 years was 34%, 46%, and 42% for DA, DAC, and FLAG-Ida, respectively. Early deaths and other adverse events were more frequent with FLAG-Ida (9% day 60 deaths\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      4% after DA or DAC;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .032). Of patients entering random assignment, 131 had MRD unknown status. In this subgroup of patients lacking evidence of residual leukemia by flow cytometry, there was no detectable survival advantage from intensification. A planned sensitivity analysis excluding these patients demonstrated a survival benefit for both DAC (HR, 0.66 [95% CI, 0.46 to 0.93];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .018) and FLAG-Ida (HR, 0.72 [95% CI, 0.53 to 0.98];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .035); OS at 3 years was 30%, 46%, and 46% for DA, DAC, and FLAG-Ida, respectively. There was a concordant reduction in relapse (DAC\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      DA: HR, 0.66 [95% CI, 0.45 to 0.98];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .039; FLAG-Ida\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      DA: HR, 0.70 [95% CI, 0.49 to 0.99];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .042). DAC benefit was maintained when survival was censored for transplant (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .042).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>In this study of older patients with AML considered fit and with evidence of residual disease after first induction, chemotherapy intensification improved survival. DAC intensification was better tolerated than FLAG-Ida.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.24.00259","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T16:46:18Z","timestamp":1761237978000},"page":"694-704","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Treatment Intensification With Either Fludarabine, AraC, G-CSF and Idarubicin, or Cladribine Plus Daunorubicin and AraC on the Basis of Residual Disease Status in Older Patients With AML: Results From the NCRI AML18 Trial"],"prefix":"10.1200","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-8155","authenticated-orcid":true,"given":"Nigel H.","family":"Russell","sequence":"first","affiliation":[{"name":"Guy's and St Thomas' NHS Foundation Trust, London, United 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