{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T07:38:26Z","timestamp":1774424306950,"version":"3.50.1"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Relapsed\/refractory RUNX1::RUNX1T1-positive acute myeloid leukemia remains a therapeutic challenge due to high relapse rates post-allogeneic hematopoietic stem cell transplantation. Preclinical evidence suggests that RUNX1::RUNX1T1 fusion proteins sensitize cells to poly ADP-ribose polymerase inhibitors by suppressing homologous recombination repair. This study explores the safety and efficacy of a novel conditioning regimen incorporating olaparib (a PARPi) for relapsed\/refractory RUNX1::RUNX1T1+ AML patients undergoing allo-HSCT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective analysis was conducted on six relapsed\/refractory RUNX1::RUNX1T1+ AML patients treated between June 2022 and October 2023 at Beijing Lu Daopei Hospital. The conditioning regimen included olaparib, FLAG, busulfan, and cyclophosphamide. Outcomes were evaluated for engraftment, toxicity, molecular remission, and survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All six patients achieved complete molecular remission within three months post transplantation. Neutrophil and platelet engraftment occurred at a median of 15 days each. Acute graft-versus-host disease occurred in four patients, and chronic GVHD was observed in all cases. Viral reactivation (CMV\/EBV) occurred in four patients. At a median follow-up of 25 months, all patients remained leukemia-free, with a 100% leukemia-free survival rate. No toxicity-related deaths or unexpected adverse events were reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The incorporation of olaparib into the conditioning regimen demonstrated favorable safety and efficacy, inducing rapid CMR and durable remission in high-risk relapsed\/refractory RUNX1::RUNX1T1+ AML patients. These findings highlight the potential of PARPi-enhanced conditioning to overcome chemotherapy resistance and reduce relapse by targeting leukemia stem cells (LSCs) through immune-mediated mechanisms. Small-sample retrospective studies have inherent limitations; hence further prospective studies are warranted to validate these results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1608899","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T05:53:55Z","timestamp":1774418035000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Augmented myeloablative conditioning with olaparib in allogeneic hematopoietic stem cell transplantation for relapsed\/refractory RUNX1::RUNX1T1-positive acute myeloid leukemia"],"prefix":"10.3389","volume":"16","author":[{"given":"Song","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Bone Marrow Transplant, Beijing Lu Daopei Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplant, Hebei Yanda Lu Daopei Hospital","place":["Langfang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Man","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Pathology & Laboratory Medicine, Beijing Lu Daopei Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui-peng","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Pathology & Laboratory Medicine, Beijing Lu Daopei Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing-yu","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplant, Hebei Yanda Lu Daopei Hospital","place":["Langfang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1038\/s41408-023-00941-4","article-title":"Risk-directed therapy based on genetics and MRD improves the outcomes of AML1-ETO-positive AML patients, a multi-center prospective cohort study","volume":"13","author":"Xu","year":"2023","journal-title":"Blood Cancer J"},{"key":"B2","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41408-021-00461-z","article-title":"The impact of the combination of KIT mutation and minimal residual disease on outcome in t(8;21) acute myeloid leukemia","volume":"11","author":"Qin","year":"2021","journal-title":"Blood Cancer J"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-11-468348","article-title":"MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in the first complete remission: results from the AML05 multicenter trial","volume":"121","author":"Zhu","year":"2013","journal-title":"Blood"},{"key":"B4","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s13045-017-0414-2","article-title":"The dynamics of RUNX1-RUNX1T1 transcript levels after allogeneic hematopoietic stem cell transplantation predict relapse in patients with t(8;21) acute myeloid leukemia","volume":"10","author":"Qin","year":"2017","journal-title":"J Hematol Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3993","article-title":"Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors","volume":"21","author":"Esposito","year":"2015","journal-title":"Nat Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-03-563403","article-title":"In adults with t(8;21)AML, posttransplant RUNX1\/RUNX1T1-based MRD monitoring, rather than c-KIT mutations, allows further risk stratification","volume":"124","author":"Wang","year":"2014","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.bbmt.2015.09.001","article-title":"International, multicenter standardization of acute graft-versus-host disease clinical data collection: A report from the mount sinai acute GVHD international consortium","volume":"22","author":"Harris","year":"2016","journal-title":"Biol Blood Marrow Transplant"},{"key":"B8","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.bbmt.2014.12.001","article-title":"National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. 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