{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T22:00:37Z","timestamp":1775167237462,"version":"3.50.1"},"reference-count":18,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"1","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Clin Cancer Inform"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Immune effector cell\u2013associated hematotoxicity (ICAHT) is a major cause of nonrelapse mortality after chimeric antigen receptor (CAR) T-cell therapy. We hypothesized that unsupervised time-series clustering could better identify archetypal patterns of early hematotoxicity compared to the early ICAHT (eICAHT) grading system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We applied unsupervised k-means time-series clustering based on Euclidean distances to longitudinal absolute neutrophil count (ANC) data from days +0 through +30 post\u2013CAR T-cell infusion in 691 patients treated at our center (training set: n = 483, 70%; test set: n = 208, 30%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Within our training set, we identified an optimal cluster solution based on four ANC recovery clusters, which were labeled as very good, good, poor, and very poor. We trained a random forest (RF) model including the top five most important features (day +3, +4, +5, +26, and +27 ANC values) to predict the cluster assignments. Within our test set, we applied the RF model to predict cluster assignments. Compared with the eICAHT criteria, the RF-predicted clusters were more compact and better separated (Dunn index: 0.078\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      0.034; average silhouette width: 0.12\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      0.010). In addition, the RF model identified patients in the good recovery cluster with intermediate overall survival (hazard ratio [HR], 1.70 [95% CI, 1.05 to 2.74];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .029; reference, very good), which was not captured by grade 2 eICAHT (HR, 1.37 [95% CI, 0.80 to 2.35];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .25; reference, grade 0-1).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Unsupervised time-series clustering identified distinct and clinically relevant patterns of hematotoxicity after CAR T-cell therapy. We trained and tested an RF model that accurately predicted cluster assignments using only five features. Predictions can be generated using our online web application.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/cci-25-00148","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T21:00:34Z","timestamp":1768424434000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Time-Series Clustering Captures Patterns of Early Immune Effector Cell\u2013Associated Hematotoxicity That Are Predictable Using Tree-Based Models"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5790-4770","authenticated-orcid":true,"given":"Emily C.","family":"Liang","sequence":"first","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"},{"name":"University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7382-5906","authenticated-orcid":true,"given":"Yein","family":"Jeon","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"},{"name":"University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6534-5304","authenticated-orcid":true,"given":"Yang","family":"Qiao","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5830-1475","authenticated-orcid":true,"given":"Xiancheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"},{"name":"University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0863-9389","authenticated-orcid":true,"given":"Jennifer J.","family":"Huang","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"},{"name":"University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1010-4578","authenticated-orcid":true,"given":"Andrew J.","family":"Portuguese","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"},{"name":"University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Basom","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0144-4906","authenticated-orcid":true,"given":"Aiko","family":"Torkelson","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5593-3314","authenticated-orcid":true,"given":"Delaney","family":"Kirchmeier","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5362-1556","authenticated-orcid":true,"given":"Kristina","family":"Braathen","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1880-7094","authenticated-orcid":true,"given":"Andrew J.","family":"Cowan","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"},{"name":"University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3365-6562","authenticated-orcid":true,"given":"Mazyar","family":"Shadman","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"},{"name":"University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7980-3882","authenticated-orcid":true,"given":"Alexandre V.","family":"Hirayama","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"},{"name":"University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian G.","family":"Till","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"},{"name":"University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1885-1773","authenticated-orcid":true,"given":"Erik L.","family":"Kimble","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"},{"name":"University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2292-4816","authenticated-orcid":true,"given":"Qian","family":"Wu","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5769-8409","authenticated-orcid":true,"given":"Jordan","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center, Seattle, WA"},{"name":"University of Washington, Seattle, 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