{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T04:05:48Z","timestamp":1776485148212,"version":"3.51.2"},"reference-count":16,"publisher":"American Society of Hematology","issue":"6","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Classical Hodgkin lymphoma (cHL) is a common malignancy in children and adolescents. Although cHL is highly curable, treatment with chemotherapy and radiation often come at the cost of long-term toxicity and morbidity. Effective risk-stratification tools are needed to tailor therapy. Here, we used gene expression profiling (GEP) to investigate tumor microenvironment (TME) biology, to determine molecular correlates of treatment failure, and to develop an outcome model prognostic for pediatric cHL. A total of 246 formalin-fixed, paraffin-embedded tissue biopsies from patients enrolled in the Children\u2019s Oncology Group trial AHOD0031 were used for GEP and compared with adult cHL data. Eosinophil, B-cell, and mast cell signatures were enriched in children, whereas macrophage and stromal signatures were more prominent in adults. Concordantly, a previously published model for overall survival prediction in adult cHL did not validate in pediatric cHL. Therefore, we developed a 9-cellular component model reflecting TME composition to predict event-free survival (EFS). In an independent validation cohort, we observed a significant difference in weighted 5-year EFS between high-risk and low-risk groups (75.2% vs 90.3%; log-rank P = .0138) independent of interim response, stage, fever, and albumin. We demonstrate unique disease biology in children and adolescents that can be harnessed for risk-stratification at diagnosis. This trial was registered at www.clinicaltrials.gov as #NCT00025259.<\/jats:p>","DOI":"10.1182\/blood.2021011941","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T21:00:17Z","timestamp":1634763617000},"page":"889-893","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":17,"title":["A gene expression\u2013based model predicts outcome in children with intermediate-risk classical Hodgkin lymphoma"],"prefix":"10.1182","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7503-9514","authenticated-orcid":false,"given":"Rebecca L.","family":"Johnston","sequence":"first","affiliation":[{"name":"1British Columbia Cancer Centre for Lymphoid Cancer, Vancouver, BC, Canada;"},{"name":"2Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane, QLD, Australia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Mottok","sequence":"additional","affiliation":[{"name":"1British Columbia Cancer Centre for Lymphoid Cancer, Vancouver, BC, Canada;"},{"name":"3Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada;"},{"name":"4Institute of Pathology, University Hospital Giessen and Marburg GmbH, Giessen, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fong Chun","family":"Chan","sequence":"additional","affiliation":[{"name":"1British Columbia Cancer Centre for Lymphoid Cancer, Vancouver, BC, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aixiang","family":"Jiang","sequence":"additional","affiliation":[{"name":"1British Columbia Cancer Centre for Lymphoid Cancer, Vancouver, BC, Canada;"},{"name":"3Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9239-1050","authenticated-orcid":false,"given":"Arjan","family":"Diepstra","sequence":"additional","affiliation":[{"name":"5Department of Pathology & Medical Biology, University of Groningen, Groningen, The Netherlands;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Visser","sequence":"additional","affiliation":[{"name":"5Department of Pathology & Medical Biology, University of Groningen, Groningen, The Netherlands;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ad\u00e8le","family":"Telenius","sequence":"additional","affiliation":[{"name":"1British Columbia Cancer Centre for Lymphoid Cancer, Vancouver, BC, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randy D.","family":"Gascoyne","sequence":"additional","affiliation":[{"name":"1British Columbia Cancer Centre for Lymphoid Cancer, Vancouver, BC, Canada;"},{"name":"3Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra L.","family":"Friedman","sequence":"additional","affiliation":[{"name":"6Department of Pediatrics, Vanderbilt-Ingram Cancer Center, Nashville, TN;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy L.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"7Pediatric Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kara M.","family":"Kelly","sequence":"additional","affiliation":[{"name":"8Department of Pediatric Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Scott","sequence":"additional","affiliation":[{"name":"1British Columbia Cancer Centre for Lymphoid Cancer, Vancouver, BC, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8293-4242","authenticated-orcid":false,"given":"Terzah M.","family":"Horton","sequence":"additional","affiliation":[{"name":"9Department of Pediatrics, Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Steidl","sequence":"additional","affiliation":[{"name":"1British Columbia Cancer Centre for Lymphoid Cancer, Vancouver, BC, Canada;"},{"name":"3Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"issue":"12","key":"2023012517142032600_B1","doi-asserted-by":"crossref","first-page":"e2027738","DOI":"10.1001\/jamanetworkopen.2020.27738","article-title":"Trends in cancer incidence in US adolescents and young adults, 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