{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:46:35Z","timestamp":1761061595619,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T00:00:00Z","timestamp":1647129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The objective of this study was to identify prognostic factors for children and adolescents with relapsed or progressive classical Hodgkin\u2019s lymphoma (cHL) to design salvage therapy tailored to them. We analyzed a homogeneous pediatric population, diagnosed with progressive\/relapsed cHL previously enrolled in two subsequent protocols of the Italian Association of Pediatric Hematology and Oncology in the period 1996\u20132016. There were 272 eligible patients, 17.5% of treated patients with cHL. Overall survival (OS) and event-free survival (EFS) after a 10-year follow-up were 65.3% and 53.3%, respectively. Patients with progressive disease (PD), advanced stage at recurrence, and \u22655 involved sites showed a significantly worse OS. PD, advanced stage, and extra-nodal involvement at recurrence were significantly associated with a poorer EFS. Multivariable analysis identified three categories for OS based on the type of recurrence and number of localizations: PD and \u22655 sites: OS 34%; PD and &lt;5 sites: OS 56.5%; relapses: OS 73.6%. Four categories were obtained for EFS based on the type of recurrence and stage: PD and stage 3\u20134: EFS 25.5%; PD and stage 1\u20132: EFS 43%; relapse and stage 3\u20134: EFS 55.4%; relapse and stage 1\u20132: EFS 72.1%. Patients with PD, in advanced stage, or with \u22655 involved sites had a very poor survival and they should be considered refractory to first- and second-line standard chemotherapy. Probably, they should be considered for more innovative approaches since the first progression. Conversely, patients who relapsed later with localized disease had a better prognosis, and they could be considered for a conservative approach.<\/jats:p>","DOI":"10.3390\/cancers14061471","type":"journal-article","created":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T22:29:43Z","timestamp":1647210583000},"page":"1471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Outcome of Children and Adolescents with Recurrent Classical Hodgkin Lymphoma: The Italian Experience"],"prefix":"10.3390","volume":"14","author":[{"given":"Alberto","family":"Garaventa","sequence":"first","affiliation":[{"name":"Paediatric Oncology Unit, IRCCS Istituto Giannina Gaslini, L.go G. Gaslini 5, 16147 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9193-1622","authenticated-orcid":false,"given":"Stefano","family":"Parodi","sequence":"additional","affiliation":[{"name":"Epidemiology and Biostatistics Unit, IRCCS Istituto Giannina Gaslini, L.go G. Gaslini 5, 16147 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Guerrini","sequence":"additional","affiliation":[{"name":"UOC Pediatria e Neonatologia, Grosseto USL-Toscana Sud-Est, Via Senese, 58100 Grosseto, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3412-0399","authenticated-orcid":false,"given":"Piero","family":"Farruggia","sequence":"additional","affiliation":[{"name":"Paediatric Haematology and Oncology Unit, A.R.N.A.S. Civic Hospital, Piazza Leotta Nicola 4, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6807-9806","authenticated-orcid":false,"given":"Alessandra","family":"Sala","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Ospedale San Gerardo, University of Milano-Bicocca, Fondazione MBBM, Via Cadore, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1190-3198","authenticated-orcid":false,"given":"Marta","family":"Pillon","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncoematologia Pediatrica, Universit\u00e0 di Padova, Via Gattamelata 5687, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Buffardi","sequence":"additional","affiliation":[{"name":"Paediatric Haemato-Oncology Department, Santobono-Pausilipon Children\u2019s Hospital, Via Mario Fiore 6, 80129 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Rossi","sequence":"additional","affiliation":[{"name":"Dipartimento di Pediatria II Ateneo di Napoli, Servizio di Oncologia Pediatrica, Via Luigi De Crecchio 2, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Pediatric Onco-Hematology and Stem Cell Transplant Division, City of Health and Science, Regina Margherita Children\u2019s Hospital, Piazza Polonia 94, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8818-1744","authenticated-orcid":false,"given":"Marco","family":"Zecca","sequence":"additional","affiliation":[{"name":"Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2803-992X","authenticated-orcid":false,"given":"Luciana","family":"Vinti","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology and Stem Cell Transplantation, Bambino Ges\u00f9 Children\u2019s Hospital, Piazza di Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Facchini","sequence":"additional","affiliation":[{"name":"Pediatric Oncology and Hematology Unit \u201cLallaSer\u00e0gnoli\u201d, Department of Pediatrics, University of Bologna, Sant\u2019Orsola Malpighi Hospital, Via Giuseppe Massarenti 9, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso","family":"Casini","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology\/Hematology, Meyer University Children\u2019s Hospital, Via Gaetano Pieraccini 24, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayla","family":"Bernasconi","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Oncology, Bone Marrow Transplant, S. Chiara University Hospital of Pisa, Via Bonanno Pisano 93, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1950-4754","authenticated-orcid":false,"given":"Loredana","family":"Amoroso","sequence":"additional","affiliation":[{"name":"Paediatric Oncology Unit, IRCCS Istituto Giannina Gaslini, L.go G. Gaslini 5, 16147 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Paediatric Haemato-Oncology Unit, Department of Clinical and Experimental Medicine, University of Catania, Piazza Universit\u00e0 2, 95124 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Provenzi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Civic Hospital, Piazza OMS 1, 24127 Bergamo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaela","family":"De Santis","sequence":"additional","affiliation":[{"name":"IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Viale Cappuccini, 47156 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Sau","sequence":"additional","affiliation":[{"name":"Pediatric Hematology-Oncology Unit, Ospedale Civico, Via Fonte Romana 8, 65124 Pescara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8813-3200","authenticated-orcid":false,"given":"Paola","family":"Muggeo","sequence":"additional","affiliation":[{"name":"Department of Biomedicine of Developmental Age, University of Bari, Piazza Umberto I 1, 70121 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa Maria","family":"Mura","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncohaematology, Microcitemico Hospital, Via Edward Jenner 18, 09121 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0571-8460","authenticated-orcid":false,"given":"Riccardo","family":"Haupt","sequence":"additional","affiliation":[{"name":"Epidemiology and Biostatistics Unit, IRCCS Istituto Giannina Gaslini, L.go G. Gaslini 5, 16147 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2828-0257","authenticated-orcid":false,"given":"Maurizio","family":"Mascarin","sequence":"additional","affiliation":[{"name":"AYA Oncology and Pediatric Radiotherapy Unit, CRO-Centro di Riferimento Oncologico di Aviano, IRCCS Aviano, Via Franco Gallini 2, 33081 Aviano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8437-1954","authenticated-orcid":false,"given":"Roberta","family":"Burnelli","sequence":"additional","affiliation":[{"name":"Pediatric Hemato-Oncology Unit, Azienda Ospedaliero Universitaria Sant\u2019Anna di Ferrara, Cona, Via Aldo Moro, 44124 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1200\/JCO.2011.40.7841","article-title":"Surveillance Computed Tomography Imaging and Detecting of Relapse in Intermediate-and Advanced-Stage Pediatric Hodgkin\u2019s Lymphoma: A Report from the Children\u2019s Oncology Group","volume":"30","author":"Voss","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e329","DOI":"10.1097\/HS9.0000000000000329","article-title":"Risk and Response Adapted Treatment Guidelines for Managing First Relapsed and Refractory Classical Hodgkin Lymphoma in Children and Young People. Recommendations from the EuroNet Pediatric Hodgkin Lymphoma Group","volume":"4","author":"Daw","year":"2020","journal-title":"HemaSphere"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/hon.2589","article-title":"Treating Hodgkin lymphoma in the new millennium: Relapsed and refractory disease","volume":"37","year":"2019","journal-title":"Hematol. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.bbmt.2018.07.038","article-title":"Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies: Expanded Analysis and Long-Term Follow-Up","volume":"25","author":"Warlick","year":"2019","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1016\/S0140-6736(15)60165-9","article-title":"Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin\u2019s lymphoma at risk of relapse or progression (AETHERA): A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"385","author":"Moskowitz","year":"2015","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1111\/bjh.16844","article-title":"Risk stratification and prognostic biomarkers in relapsed Hodgkin lymphoma","volume":"190","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6181","DOI":"10.1200\/JCO.2005.07.930","article-title":"Salvage therapy of progressive and recurrent Hodgkin\u2019s disease: Results from a multicenter study of the pediatric DAL\/GPOH-HD study group","volume":"23","author":"Schellong","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Burnelli, R., Fiumana, G., Rondelli, R., Pillon, M., Sala, A., Garaventa, A., D\u2019Amore, E.S.G., Sabattini, E., Buffardi, S., and Bianchi, M. (2020). Comparison of Hodgkin\u2019s Lymphoma in Children and Adolescents. A Twenty Year Experience with MH\u201996 and LH2004 AIEOP (Italian Association of Pediatric Hematology and Oncology) Protocols. Cancers, 12.","DOI":"10.3390\/cancers12061620"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1182\/blood-2016-01-643569","article-title":"The 2016 revision of the World Health Organization classification of lymphoid neoplasms","volume":"127","author":"Swerdlow","year":"2016","journal-title":"Blood"},{"key":"ref_10","first-page":"1028","article-title":"High-dose infusional ifosfamide, etoposide plus methylprednisolone followed by dexamethasone, high-dose ara-C and cisplatinum and autologous stem cell transplantation for refractory or relapsed aggressive non-Hodgkin\u2019s lymphoma","volume":"87","author":"Salar","year":"2002","journal-title":"Haematologica"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/sj.leu.2402402","article-title":"Long-term follow-up of short intensive multiagent chemotherapy without high-dose methotrexate (\u2018Orange\u2019) in children with advanced non-lymphoblastic non-Hodgkin\u2019s lymphoma: A children\u2019s cancer group report","volume":"16","author":"Cairo","year":"2002","journal-title":"Leukemia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1023\/A:1008396525292","article-title":"High-dose BEAM chemotherapy with autologous peripheral blood progenitor-cell transplantation for unselected patients with primary refractory or relapsed Hodgkin\u2019s disease","volume":"11","author":"Argiris","year":"2000","journal-title":"Ann. Oncol."},{"key":"ref_13","unstructured":"Hosmer, D.W., and Lemeshow, S. (1999). Applied Survival Analysis\u2014Regression Modelling of Time to Event Data, John Wiley & Sons, Inc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1002\/pbc.24568","article-title":"Relapse after treatment of pediatric Hodgkin lymphoma: Outcome and role of surveillance after end of therapy","volume":"60","author":"Friedmann","year":"2013","journal-title":"Pediatric Blood Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/bjc.1992.426","article-title":"Outcome of children with resistant and relapsed Hodgkin\u2019s disease","volume":"66","author":"James","year":"1992","journal-title":"Br. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4376","DOI":"10.1002\/cncr.25225","article-title":"Initial response to salvage therapy determines prognosis in relapsed pediatric Hodgkin lymphoma patients","volume":"116","author":"Metzger","year":"2010","journal-title":"Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Camus, V., and Jardin, F. (2021). Cell-Free DNA for the Management of Classical Hodgkin Lymphoma. Pharmaceuticals, 14.","DOI":"10.3390\/ph14030207"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"364","DOI":"10.7150\/jca.13593","article-title":"Kinetics of Circulating Plasma Cell-Free DNA in Paediatric Classical Hodgkin Lymphoma","volume":"7","author":"Primerano","year":"2016","journal-title":"J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1182\/bloodadvances.2020003039","article-title":"The landscape of copy number variations in classical Hodgkin lymphoma: A joint KU Leuven and LYSA study on cell-free DNA","volume":"5","author":"Buedts","year":"2021","journal-title":"Blood Adv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e450","DOI":"10.1016\/S2352-3026(18)30153-4","article-title":"Brentuximab vedotin for paediatric relapsed or refractory Hodgkin\u2019s lymphoma and anaplastic large-cell lymphoma: A multicentre, open-label, phase 1\/2 study","volume":"5","author":"Locatelli","year":"2018","journal-title":"Lancet Haematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/S1470-2045(18)30426-1","article-title":"Brentuximab-vedotin with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin\u2019s lymphoma (AHOD1221): A Children\u2019s Oncology Group, multicentre single-arm, phase 1\u20132 trial","volume":"19","author":"Cole","year":"2018","journal-title":"Lancet Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/6\/1471\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:35:53Z","timestamp":1760135753000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/6\/1471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,13]]},"references-count":21,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["cancers14061471"],"URL":"https:\/\/doi.org\/10.3390\/cancers14061471","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2022,3,13]]}}}