{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:35:37Z","timestamp":1768566937479,"version":"3.49.0"},"posted":{"date-parts":[[2023,8,21]]},"group-title":"Hematology","reference-count":12,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,8,21]]},"abstract":"Abstract<\/jats:title>\n \n The presence of measurable residual disease (MRD) prior to an allogeneic hematopoietic transplant (alloHCT) in Acute Myeloid Leukemia (AML) has been shown to be associated with an increased risk of post-transplant relapse. Since the Isocitrate Dehydrogenase genes (\n IDH1<\/jats:italic>\n \/\n 2<\/jats:italic>\n ) are mutated in a considerable proportion of patients with AML, we studied if these mutations would serve as useful targets for MRD. Fifty-five\n IDH<\/jats:italic>\n -mutated AML patients undergoing non-myeloablative alloHCT with post-transplant cyclophosphamide at a single center were sequenced at baseline using a multi-gene panel followed by targeted testing for persistent\n IDH<\/jats:italic>\n mutations at the pre- and post-alloHCT timepoints by digital droplet PCR or error-corrected next generation sequencing. The cohort included patients who had been treated with\n IDH<\/jats:italic>\n inhibitors pre- and post-transplant (20% and 17% for\n IDH1<\/jats:italic>\n and 38% and 28% for\n IDH2<\/jats:italic>\n ). Overall, 55% of patients analyzed had detectable\n IDH<\/jats:italic>\n mutations during complete remission prior to alloHCT. However, there were no statistically significant differences in overall survival (OS), relapse-free survival (RFS), and cumulative incidence of relapse (CIR) at 3 years between patients who tested positive or negative for a persistent\n IDH<\/jats:italic>\n mutation during remission (OS:\n IDH1<\/jats:italic>\n p=1,\n IDH2<\/jats:italic>\n p=0.87; RFS:\n IDH1<\/jats:italic>\n p=0.71,\n IDH2<\/jats:italic>\n p= 0.78; CIR:\n IDH1<\/jats:italic>\n p=0.92,\n IDH2<\/jats:italic>\n p=0.97). There was also no difference in the prevalence of persistent\n IDH<\/jats:italic>\n mutation between patients who did and did not receive an\n IDH<\/jats:italic>\n inhibitor (p=0.59). Mutational profiling of available relapse samples showed that 8 out of 9 patients still exhibited the original\n IDH<\/jats:italic>\n mutation, indicating that the\n IDH<\/jats:italic>\n mutations remained stable through the course of the disease. This study demonstrates that persistent\n IDH<\/jats:italic>\n mutations during remission is not associated with inferior clinical outcomes after alloHCT in patients with AML.\n <\/jats:p>","DOI":"10.1101\/2023.08.14.23294087","type":"posted-content","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T18:40:47Z","timestamp":1692643247000},"source":"Crossref","is-referenced-by-count":1,"title":["Persistent\n IDH<\/i>\n mutations are not associated with increased relapse or death in patients with\n IDH<\/i>\n -mutated acute myeloid leukemia undergoing allogeneic hematopoietic cell transplant with post-transplant cyclophosphamide"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2550-493X","authenticated-orcid":false,"given":"Niveditha","family":"Ravindra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura W.","family":"Dillon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gege","family":"Gui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukasz P.","family":"Gondek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Corner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6189-8067","authenticated-orcid":false,"given":"Christopher S.","family":"Hourigan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander J.","family":"Ambinder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"12","key":"2023082313450860000_2023.08.14.23294087v1.1","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1038\/s41375-022-01692-0","article-title":"Association of hematologic response and assay sensitivity on the prognostic impact of measurable residual disease in acute myeloid leukemia: a systematic review and meta-analysis","volume":"36","year":"2022","journal-title":"Leukemia"},{"key":"2023082313450860000_2023.08.14.23294087v1.2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.159343"},{"issue":"9","key":"2023082313450860000_2023.08.14.23294087v1.3","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1001\/jama.2023.1363","article-title":"DNA Sequencing to Detect Residual Disease in Adults With Acute Myeloid Leukemia Prior to Hematopoietic Cell Transplant","volume":"329","year":"2023","journal-title":"JAMA"},{"key":"2023082313450860000_2023.08.14.23294087v1.4","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021013626"},{"key":"2023082313450860000_2023.08.14.23294087v1.5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-693879"},{"issue":"1","key":"2023082313450860000_2023.08.14.23294087v1.6","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s13045-022-01339-8","article-title":"Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation","volume":"15","year":"2022","journal-title":"Journal of Hematology & Oncology"},{"issue":"20","key":"2023082313450860000_2023.08.14.23294087v1.7","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.1182\/blood.2020010165","article-title":"Prognostic significance of concurrent gene mutations in intensively treated patients with IDH-mutated AML: an ALFA study","volume":"137","year":"2021","journal-title":"Blood"},{"issue":"4","key":"2023082313450860000_2023.08.14.23294087v1.8","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.clml.2021.09.022","article-title":"Nonmyeloablative Allogeneic Transplantation With Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia With IDH Mutations: A Single Center Experience","volume":"22","year":"2022","journal-title":"Clin Lymphoma Myeloma Leuk"},{"issue":"3","key":"2023082313450860000_2023.08.14.23294087v1.9","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1182\/bloodadvances.2021005789","article-title":"Impact of IDH1 and IDH2 mutation detection at diagnosis and in remission in patients with AML receiving allogeneic transplantation","volume":"7","year":"2023","journal-title":"Blood Adv"},{"key":"2023082313450860000_2023.08.14.23294087v1.10","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.191148"},{"key":"2023082313450860000_2023.08.14.23294087v1.11","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-99-110449"},{"key":"2023082313450860000_2023.08.14.23294087v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/nature13038"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.08.14.23294087","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:39:05Z","timestamp":1768505945000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2023.08.14.23294087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,21]]},"references-count":12,"URL":"https:\/\/doi.org\/10.1101\/2023.08.14.23294087","relation":{},"subject":[],"published":{"date-parts":[[2023,8,21]]},"subtype":"preprint"}}