{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:35:10Z","timestamp":1768570510302,"version":"3.49.0"},"posted":{"date-parts":[[2025,11,17]]},"group-title":"Oncology","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The prognostic value of nucleophosmin-1 (\n                  <jats:italic>NPM1<\/jats:italic>\n                  ) and fms-like tyrosine kinase 3 (\n                  <jats:italic>FLT3<\/jats:italic>\n                  ) mutations has been well-established in adult patients but is less clear in geriatric patients. This retrospective cohort study assessed adult patients with acute myeloid leukemia (AML) who received\n                  <jats:italic>FLT3<\/jats:italic>\n                  and\/or\n                  <jats:italic>NPM1<\/jats:italic>\n                  testing treated at any Veterans Health Administration (VHA) facility or at Vanderbilt University Medical Center (VUMC) between January 2006 and December 2016. The primary analysis compared time to all-cause death among patients with AML based on\n                  <jats:italic>FLT3<\/jats:italic>\n                  and\n                  <jats:italic>NPM1<\/jats:italic>\n                  mutation status, age (&lt;65 years, \u226565 years), and cytogenetic risk group (unfavorable, intermediate\/normal, favorable). The study population (n=766) (mean age 59.71 \u00b1 16.6 years, 45.96% \u226565 years) had a mutation rate of 19.8% for\n                  <jats:italic>FLT3<\/jats:italic>\n                  and 22.1% for\n                  <jats:italic>NPM1<\/jats:italic>\n                  . Age was a significant factor in overall survival (median OS: 24.28 vs. 8.18 months, p&lt;0.001), as was cytogenetic risk status (median OS: favorable group not reached, intermediate\/normal 17.61m vs. unfavorable 6.77m, p&lt;0.001). The most favorable prognostic group (\n                  <jats:italic>FLT3<\/jats:italic>\n                  -\/\n                  <jats:italic>NPM1<\/jats:italic>\n                  +) among older patients showed worse OS (15.21 months) than did the poor prognostic group (\n                  <jats:italic>NPM1<\/jats:italic>\n                  -\/\n                  <jats:italic>FLT3<\/jats:italic>\n                  -) among younger patients (18.43 months). Among the older cohort,\n                  <jats:italic>FLT3<\/jats:italic>\n                  and\n                  <jats:italic>NPM1<\/jats:italic>\n                  mutation status, favorable karyotype, and CCI were not identified as prognostic factors. In the full cohort, using Cox proportional hazard regression and LASSO analyses for age,\n                  <jats:italic>FLT3<\/jats:italic>\n                  and\n                  <jats:italic>NPM1<\/jats:italic>\n                  mutation status, cytogenetic risk group, treatment site, race, primary payor, and Charleston Comorbidity Index (CCI), age (HR 65y vs 35y\/=2.44, 95% CI 1.61-3.68, p&lt;0.001) was the strongest risk factor in AML.\n                <\/jats:p>","DOI":"10.1101\/2025.11.16.25340236","type":"posted-content","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T07:50:13Z","timestamp":1763452213000},"source":"Crossref","is-referenced-by-count":0,"title":["Differences in prognostic value of\n                  <i>FLT3<\/i>\n                  and\n                  <i>NPM1<\/i>\n                  mutations in older and younger patient populations with acute myeloid leukemia"],"prefix":"10.64898","author":[{"given":"Claudio A.","family":"Mosse","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"LeNoue-Newton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0108-2127","authenticated-orcid":false,"given":"Julie A.","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy M.","family":"Perkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fern","family":"Fitzhenry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn M.","family":"Pridgen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Freneka","family":"Minter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mia","family":"Levy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3217-4147","authenticated-orcid":false,"given":"Michael E.","family":"Matheny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025111923450424000_2025.11.16.25340236v1.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21387"},{"key":"2025111923450424000_2025.11.16.25340236v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28129"},{"key":"2025111923450424000_2025.11.16.25340236v1.3","unstructured":"Noone A , Howlader N , Krapcho M , et al. 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