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Quantitative polymerase chain reaction (qPCR) is the preferred MRD platform but unfortunately, 40%\u201360% of AML patients have no high\u2010quality qPCR target. This study aimed to improve MRD testing by utilising droplet digital PCR (ddPCR). ddPCR offers patient\u2010specific monitoring but concerns of tracking clonal haematopoiesis rather than malignant cells prompt further validation.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Retrospectively, we performed MRD testing on blood and bone marrow samples from AML patients transplanted by reduced\u2010intensity conditioning.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The applicability of ddPCR was 39\/42 (92.9%). Forty\u2010five ddPCR assays were validated with a 0.0089% median sensitivity. qPCR targeting\n NPM1<\/jats:italic>\n mutation detected relapse 46\u2009days before ddPCR (\n p<\/jats:italic>\n \u2009=\u2009.03). ddPCR detected relapse 34.5\u2009days before qPCR targeting\n WT1<\/jats:italic>\n overexpression (\n p<\/jats:italic>\n \u2009=\u2009.03). In non\u2010relapsing patients, zero false positive ddPCR MRD relapses were observed even when monitoring targets associated with clonal haematopoiesis such as\n DNMT3A<\/jats:italic>\n ,\n TET2<\/jats:italic>\n , and\n ASXL1<\/jats:italic>\n mutations.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These results confirm that qPCR targeting\n NPM1<\/jats:italic>\n mutations or fusion transcripts are superior in MRD testing. In the absence of such targets, ddPCR is a promising alternative demonstrating (a) high applicability, (b) high sensitivity, and (c) zero false positive MRD relapses in non\u2010relapsing patients.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ejh.14151","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T08:19:20Z","timestamp":1704874760000},"page":"601-610","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Droplet digital\n PCR<\/scp>\n for sensitive relapse detection in acute myeloid leukaemia patients transplanted by reduced intensity conditioning"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1195-907X","authenticated-orcid":false,"given":"Jonas Kassow","family":"Gronlund","sequence":"first","affiliation":[{"name":"Department of Haematology Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1531-1862","authenticated-orcid":false,"given":"Christopher","family":"Veigaard","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2000-8290","authenticated-orcid":false,"given":"Caroline","family":"Juhl\u2010Christensen","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3859-9544","authenticated-orcid":false,"given":"Anne\u2010Sofie","family":"Skou","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2336-8089","authenticated-orcid":false,"given":"Dorte","family":"Melsvik","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-8694","authenticated-orcid":false,"given":"Hans Beier","family":"Ommen","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17213"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001728"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2014.08.016"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1507471"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021013626"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30580-1"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.12524"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2020.09.020"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11030483"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-09-801498"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.16.9236"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02217-x"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2020.1755855"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2018.08.012"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.183525"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12071738"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.135467"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9010271"},{"issue":"6","key":"e_1_2_11_20_1","first-page":"1304","article-title":"Digital droplet PCR in hematologic malignancies: a new useful molecular tool","volume":"12","author":"Galimberti S","year":"2022","journal-title":"Diagnostics (Basel)"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2018-0827"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-157802"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17449"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.4865"},{"key":"e_1_2_11_25_1","unstructured":"ddPCR\u2122 Rare Mutation Detection.2021[cited 2023; 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