{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:51:20Z","timestamp":1790351480281,"version":"4.1.0"},"reference-count":18,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["848101002"],"award-info":[{"award-number":["848101002"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Approximately 40%\u201360% of patients reaching a stable deep molecular response during TKI treatment will maintain a state of remission after TKI discontinuation, denoted as treatment\u2010free remission (TFR). Depth of molecular response assessed by <jats:italic>BCR::ABL1<\/jats:italic> digital PCR prior to TKI discontinuation has demonstrated its significance as a reliable predictive parameter for TFR. A clinically applicable prediction cutoff of 0.0023%IS has been established and externally validated. In this study, <jats:italic>BCR::ABL1<\/jats:italic> digital PCR, as most sensitive and stable assay of its kind, was investigated as a TFR prediction tool in the Netherlands, and evaluated for its predictive value to stop TKI treatment below the aforementioned cutoff. The primary endpoint of molecular recurrence (MolR, <jats:italic>BCR::ABL1<\/jats:italic>\u2009&gt;\u20090.1%IS) at 12\u2009months was prospectively assessed. Overall, 67 discontinued patients below the set <jats:italic>BCR::ABL1<\/jats:italic> digital PCR cutoff were included. The overall MolR probability was 50% (95% CI, 36%\u201362%). In 38 patients treated for more than 6\u2009years as commonly recommended as desirable treatment duration before TFR attempt, the MolR probability dropped to 36% (95% CI, 18%\u201350%). Patients attempting an early TKI discontinuation (treated for less than 6\u2009years) had a high MolR probability of 76% (95% CI, 65%\u201389%). <jats:italic>BCR::ABL1<\/jats:italic> digital PCR was successfully used in Dutch clinical practice. Our study indicates that in patients with a low <jats:italic>BCR::ABL1<\/jats:italic> digital PCR result, a total TKI treatment duration of six or more years remains associated with a lower MolR rate and should generally be pursued. In patients treated for more than 6\u2009years, <jats:italic>BCR::ABL1<\/jats:italic> digital PCR was capable to identify stop candidates with a higher probability of TFR success.<\/jats:p>","DOI":"10.1111\/ejh.14368","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T03:09:01Z","timestamp":1739761741000},"page":"900-907","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Treatment\u2010Free Remission Outcomes in a <i><scp>BCR<\/scp>::<scp>ABL1<\/scp><\/i> Digital <scp>PCR<\/scp> Selected Clinical Cohort of <scp>CML<\/scp> Patients"],"prefix":"10.1111","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6198-7035","authenticated-orcid":false,"given":"C.","family":"Kockerols","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Albert Schweitzer Hospital  Dordrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. J. M.","family":"Valk","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Hogenbirk","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9470-476X","authenticated-orcid":false,"given":"I.","family":"Geelen","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. M. A.","family":"Blijlevens","sequence":"additional","affiliation":[{"name":"Department of Hematology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. J. W. M.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Hematology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Hoogendoorn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Medisch Centrum Leeuwarden  Leeuwarden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Kersting","sequence":"additional","affiliation":[{"name":"Department of Hematology Haga Ziekenhuis  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. K.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Hematology University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. G. M.","family":"Daenen","sequence":"additional","affiliation":[{"name":"Department of Hematology University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Donker","sequence":"additional","affiliation":[{"name":"Department of Hematology University Medical Center Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. A. W.","family":"te Boekhorst","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.\u2010S. G.","family":"Jie","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Zuyderland Medisch Centrum  Sittard\u2010Geleen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Corsten","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Meander Medisch Centrum  Amersfoort The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J.","family":"Cruijsen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Catharina Ziekenhuis  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Levenga","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Groene Hart Ziekenhuis  Gouda The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. M.","family":"Smit","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Medisch Spectrum Twente  Enschede The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.\u2010D.","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Albert Schweitzer Hospital  Dordrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"de Jongh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Albert Schweitzer Hospital  Dordrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Canisius Wilhelmina Ziekenhuis  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. J.","family":"Vlot","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Rijnstate Ziekenhuis  Arnhem The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. F.","family":"Durian","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Elizabeth Tweesteden Ziekenhuis  Tilburg The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. J.","family":"Zwaginga","sequence":"additional","affiliation":[{"name":"Department of Hematology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Mohlmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Isala  Zwolle The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. J.","family":"Wustman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Wilhelmina Ziekenhuis Assen  Assen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Blommers","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Albert Schweitzer Hospital  Dordrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. J.","family":"Cornelissen","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0746-7039","authenticated-orcid":false,"given":"P. E.","family":"Westerweel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Albert Schweitzer Hospital  Dordrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Collaborating Authors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.66.2866"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0776-2"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30192-X"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70233-3"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16408"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.5774"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.194894"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-017-2334-x"},{"issue":"6","key":"e_1_2_10_10_1","article-title":"Digital PCR for BCR\u2010ABL1 Quantification in CML: Current Applications in Clinical Practice","volume":"4","author":"Kockerols C. C. B.","year":"2020","journal-title":"Hema"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24120"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.139899"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-3373"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2087"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.18277"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2650"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27359"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.14271"},{"key":"e_1_2_10_19_1","first-page":"326","article-title":"Achtergronden bij de richtlijn voor de behandeling van chronische myelo\u00efde leukemie anno 2018 deel 3: stoppen van de behandeling, beleid bij zwangerschap, studies en therapie\u2010aanbevelingen","volume":"15","author":"Janssen J. J. W. M.","year":"2018","journal-title":"Ned TIJDSCHR HEMATOL"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.14368","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T12:08:38Z","timestamp":1754914118000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejh.14368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,17]]},"references-count":18,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1111\/ejh.14368"],"URL":"https:\/\/doi.org\/10.1111\/ejh.14368","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,17]]},"assertion":[{"value":"2024-08-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}