{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T20:28:07Z","timestamp":1783024087004,"version":"3.54.6"},"reference-count":24,"publisher":"American Society of Hematology","issue":"25","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,12,19]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Deuterated (\u201cheavy\u201d) water labeling in patients with chronic lymphocytic leukemia (CLL) demonstrates that IGHV unmutated and ZAP-70+ patients have higher blood and tissue CLL death rates on ibrutinib therapy, resulting in lower measurable residual disease levels with long-term ibrutinib treatment. This trial was registered at www.clinicaltrials.gov as #NCT01752426.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024025683","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T17:54:37Z","timestamp":1729706077000},"page":"2678-2681","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":4,"title":["Deuterated water labeling in ibrutinib-treated patients with CLL: leukemia cell kinetics correlate with <i>IGHV<\/i>, ZAP-70, and MRD"],"prefix":"10.1182","volume":"144","author":[{"given":"Ekaterina","family":"Kim","sequence":"first","affiliation":[{"name":"1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Shih","family":"Chen","sequence":"additional","affiliation":[{"name":"2Karches Center for Oncology Research, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela","family":"Sivina","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunsoo","family":"Hwang","sequence":"additional","affiliation":[{"name":"3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1192-9336","authenticated-orcid":false,"given":"Xuelin","family":"Huang","sequence":"additional","affiliation":[{"name":"3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9547-4193","authenticated-orcid":false,"given":"Alessandra","family":"Ferrajoli","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0114-8384","authenticated-orcid":false,"given":"Nitin","family":"Jain","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7357-270X","authenticated-orcid":false,"given":"William G.","family":"Wierda","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8017-3707","authenticated-orcid":false,"given":"Dominik","family":"Wodarz","sequence":"additional","affiliation":[{"name":"4Department of Mathematics and Department of Ecology and Evolutionary Biology, University of California, Irvine, Irvine, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1023-6650","authenticated-orcid":false,"given":"Nicholas","family":"Chiorazzi","sequence":"additional","affiliation":[{"name":"2Karches Center for Oncology Research, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY"},{"name":"5Zucker School of Medicine at Hofstra\/Northwell, Hempstead, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6177-7572","authenticated-orcid":false,"given":"Jan A.","family":"Burger","sequence":"additional","affiliation":[{"name":"1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"2","key":"2024121916205343200_bib1","doi-asserted-by":"crossref","first-page":"e89904","DOI":"10.1172\/jci.insight.89904","article-title":"Leukemia cell proliferation and death\u00a0in chronic lymphocytic leukemia patients on therapy with the\u00a0BTK\u00a0inhibitor ibrutinib","volume":"2","author":"Burger","year":"2017","journal-title":"JCI Insight"},{"issue":"5","key":"2024121916205343200_bib2","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1056\/NEJMra1908213","article-title":"Treatment of chronic lymphocytic leukemia","volume":"383","author":"Burger","year":"2020","journal-title":"N\u00a0Engl J Med"},{"issue":"3","key":"2024121916205343200_bib3","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/s41375-019-0602-x","article-title":"Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL\/SLL: 5 years of follow-up\u00a0from the phase 3 RESONATE-2 study","volume":"34","author":"Burger","year":"2020","journal-title":"Leukemia"},{"issue":"6","key":"2024121916205343200_bib4","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1182\/blood.V94.6.1848","article-title":"Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia","volume":"94","author":"Hamblin","year":"1999","journal-title":"Blood"},{"issue":"6","key":"2024121916205343200_bib5","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1182\/blood.V94.6.1840","article-title":"Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia","volume":"94","author":"Damle","year":"1999","journal-title":"Blood"},{"issue":"7","key":"2024121916205343200_bib6","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.3324\/haematol.2013.098384","article-title":"The outcome of B-cell receptor signaling in chronic lymphocytic leukemia: proliferation or anergy","volume":"99","author":"Packham","year":"2014","journal-title":"Haematologica"},{"issue":"6","key":"2024121916205343200_bib7","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1182\/blood-2016-03-707786","article-title":"Surface IgM expression and function are associated with clinical behavior, genetic abnormalities, and DNA methylation in CLL","volume":"128","author":"D'Avola","year":"2016","journal-title":"Blood"},{"issue":"3","key":"2024121916205343200_bib8","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/nrc.2017.121","article-title":"Targeting B cell receptor signalling in cancer: preclinical and clinical advances","volume":"18","author":"Burger","year":"2018","journal-title":"Nat Rev Cancer"},{"issue":"6","key":"2024121916205343200_bib9","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.4049\/jimmunol.1600915","article-title":"Functional differences between IgM and IgD signaling in chronic lymphocytic leukemia","volume":"197","author":"Ten Hacken","year":"2016","journal-title":"J\u00a0Immunol"},{"issue":"9","key":"2024121916205343200_bib10","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1056\/NEJMoa040857","article-title":"ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia","volume":"351","author":"Rassenti","year":"2004","journal-title":"N\u00a0Engl J Med"},{"issue":"5","key":"2024121916205343200_bib11","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1182\/bloodadvances.2022009557","article-title":"ZAP-70 augments tonic B-cell receptor and CCR7 signaling in IGHV-unmutated chronic lymphocytic leukemia","volume":"8","author":"Chen","year":"2024","journal-title":"Blood Adv"},{"issue":"5","key":"2024121916205343200_bib12","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1182\/blood-2006-12-062265","article-title":"ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia","volume":"111","author":"Chen","year":"2008","journal-title":"Blood"},{"issue":"5","key":"2024121916205343200_bib13","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1038\/sj.leu.2404584","article-title":"International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia","volume":"21","author":"Rawstron","year":"2007","journal-title":"Leukemia"},{"issue":"8","key":"2024121916205343200_bib14","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/modpathol.3800145","article-title":"Immunohistochemical detection of ZAP-70 in 341 cases of\u00a0non-Hodgkin and Hodgkin lymphoma","volume":"17","author":"Admirand","year":"2004","journal-title":"Mod Pathol"},{"issue":"3","key":"2024121916205343200_bib15","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1172\/JCI23409","article-title":"In\u00a0vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells","volume":"115","author":"Messmer","year":"2005","journal-title":"J\u00a0Clin Invest"},{"issue":"26","key":"2024121916205343200_bib16","doi-asserted-by":"crossref","first-page":"4132","DOI":"10.1182\/blood-2014-02-554220","article-title":"Kinetics of CLL cells in tissues and blood during therapy with the BTK inhibitor ibrutinib","volume":"123","author":"Wodarz","year":"2014","journal-title":"Blood"},{"issue":"6","key":"2024121916205343200_bib17","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1038\/leu.2017.34","article-title":"Leukemia-cell proliferation and disease progression in patients with early stage chronic lymphocytic leukemia","volume":"31","author":"Murphy","year":"2017","journal-title":"Leukemia"},{"issue":"12","key":"2024121916205343200_bib18","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1182\/blood-2013-09-527853","article-title":"Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy","volume":"123","author":"Woyach","year":"2014","journal-title":"Blood"},{"issue":"suppl 1","key":"2024121916205343200_bib19","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1182\/blood-2023-174750","article-title":"Acalabrutinib \u00b1 obinutuzumab vs obinutuzumab + chlorambucil in treatment-naive chronic lymphocytic leukemia: 6-year follow-up of Elevate-TN [abstract]","volume":"142","author":"Sharman","year":"2023","journal-title":"Blood"},{"issue":"3","key":"2024121916205343200_bib20","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1182\/blood-2015-09-667675","article-title":"Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia","volume":"127","author":"Thompson","year":"2016","journal-title":"Blood"},{"issue":"9","key":"2024121916205343200_bib21","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/S1470-2045(20)30443-5","article-title":"Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial","volume":"21","author":"Al-Sawaf","year":"2020","journal-title":"Lancet Oncol"},{"issue":"22","key":"2024121916205343200_bib22","doi-asserted-by":"crossref","first-page":"3278","DOI":"10.1182\/blood.2021014488","article-title":"Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL: primary analysis of the CAPTIVATE FD cohort","volume":"139","author":"Tam","year":"2022","journal-title":"Blood"},{"issue":"12","key":"2024121916205343200_bib23","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/S1470-2045(23)00452-7","article-title":"Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial","volume":"24","author":"Niemann","year":"2023","journal-title":"Lancet Oncol"},{"issue":"4","key":"2024121916205343200_bib24","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1056\/NEJMoa2310063","article-title":"Chronic lymphocytic leukemia therapy guided by measurable residual disease","volume":"390","author":"Munir","year":"2024","journal-title":"N\u00a0Engl J Med"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/144\/25\/2678\/2347044\/blood_bld-2024-025683-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/144\/25\/2678\/2347044\/blood_bld-2024-025683-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T16:31:34Z","timestamp":1734625894000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/144\/25\/2678\/518297\/Deuterated-water-labeling-in-ibrutinib-treated"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,19]]},"references-count":24,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2024,12,19]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2024025683","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,19]]}}}