{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:08:34Z","timestamp":1787508514829,"version":"build-2736575974"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    The study investigates how sex and age influence treatment response in paediatric, adolescent and young adult (AYA) classical Hodgkin lymphoma (cHL), integrating clinical data, immune\u2010gene profiling and metabolic imaging from the European Network for Paediatric Hodgkin Lymphoma (EuroNet\u2010PHL\u2010C2 trial). cHL patients treated in Italian Association of Pediatric Hematology &amp; Oncology Research (AIEOP)\u00a0centres (2018\u20132020) underwent fluorodeoxyglucose\u2010positron emission tomography (FDG\u2010PET) at baseline, after two chemotherapy cycles early response assessment (ERA) and post\u2010chemotherapy (late response assessment, LRA). Responses were classified as early complete metabolic response (CMR) or as adequate response (AR), inadequate (IR) or progressive disease at LRA. Tumour samples were profiled for 730 immune\u2010related genes, and clinical and quantitative positron emission tomography parameters were integrated to assess sex\u2010 and age\u2010related patterns. Sixty\u2010eight cases passed quality control. Early CMR occurred in 51.5% at ERA; 29.4% showed (AR) at LRA. Older age (\u226513\u2009years), especially in males, was associated with higher IR risk. runt\u2010related transcription factor 3 (\n                    <jats:italic>RUNX3)<\/jats:italic>\n                    expression characterized CMR; a five\u2010gene panel (Bone Marrow Stromal Cell Antigen\u20101\/CD157 [\n                    <jats:italic>BST1<\/jats:italic>\n                    ]; C\u2010X\u2010C Motif Chemokine Receptor 6 [\n                    <jats:italic>CXCR6<\/jats:italic>\n                    ]; Inducible T\u2010cell Co\u2010stimulator\/CD278 [\n                    <jats:italic>ICOS<\/jats:italic>\n                    ], Ubiquitin Specific Peptidase 9 Y\u2010Linked [\n                    <jats:italic>USP9Y<\/jats:italic>\n                    ], and Single Ig IL\u20101\u2010Related Receptor\/IL\u20101R8 [\n                    <jats:italic>SIGIRR<\/jats:italic>\n                    ]) predicted IR and reflected sex\u2010related immune differences.\n                    <jats:italic>USP9Y<\/jats:italic>\n                    expression correlated with baseline tumour volume (total metabolic tumour volume, TMTV1). Combining TMTV1 with\n                    <jats:italic>RUNX3<\/jats:italic>\n                    improved CMR discrimination, while TMTV1 with the five\u2010gene panel increased sensitivity but reduced accuracy at LRA. Sex and age influence immune response in AYA cHL.\n                    <jats:italic>RUNX3<\/jats:italic>\n                    and the five\u2010gene panel show promise as biomarkers of early and late response.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70423","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T23:24:37Z","timestamp":1773357877000},"page":"1617-1630","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunoprofiling, sex\u2010 and age\u2010related determinants of treatment response in paediatric, adolescent and young adult Hodgkin lymphoma"],"prefix":"10.1111","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6100-9373","authenticated-orcid":false,"given":"Valli","family":"De Re","sequence":"first","affiliation":[{"name":"Immunopatologia e Biomarcatori Oncologici Centro di Riferimento Oncologico di Aviano (CRO), IRCCS  Aviano 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9609-8952","authenticated-orcid":false,"given":"Angelo","family":"Vitullo","sequence":"additional","affiliation":[{"name":"Oncologia Radioterapica e Radioterapia Pediatrica Centro di Riferimento Oncologico di Aviano (CRO), IRCCS  Aviano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1418-4624","authenticated-orcid":false,"given":"Veronica","family":"Paduano","sequence":"additional","affiliation":[{"name":"Immunopatologia e Biomarcatori Oncologici Centro di Riferimento Oncologico di Aviano (CRO), IRCCS  Aviano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3794-270X","authenticated-orcid":false,"given":"Mariangela","family":"De Zorzi","sequence":"additional","affiliation":[{"name":"Immunopatologia e Biomarcatori Oncologici Centro di Riferimento Oncologico di Aviano (CRO), IRCCS  Aviano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4802-1866","authenticated-orcid":false,"given":"Lara","family":"Mussolin","sequence":"additional","affiliation":[{"name":"Clinica Emato\u2010Oncologica Pediatrica, Dipartimento di Salute della Donna e del Bambino Istituto di Ricerca Pediatrica Fondazione Citt\u00e0 della Speranza, Universit\u00e0 di Padova  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1940-7375","authenticated-orcid":false,"given":"Paola","family":"Quarello","sequence":"additional","affiliation":[{"name":"Oncoematologia Ospedale Regina Margherita  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Ematologia Ospedale Universitario Meyer  Firenze 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