Should adolescents and young adults with Hodgkin lymphoma be treated as children or adults?
Corresponding Author
Lucille Lew-Derivry
Pediatric Hematology and Oncology Department, Sorbonne University APHP, A.Trousseau Hospital, Paris, France
Correspondence
Lucille Lew-Derivry, Pediatric Hematology and Oncology Department, Sorbonne University APHP, A.Trousseau Hospital, Paris, France.
Email: [email protected]
Search for more papers by this authorFlorian Chevillon
Adolescent and Young Adults Hematology Department, St Louis Hospital, Paris, France
Search for more papers by this authorPauline Brice
Hemato-Oncology Department, St Louis Hospital, Paris, France
Search for more papers by this authorCamille Bigenwald
Hematology Department, Gustave Roussy Institute, Villejuif, France
Search for more papers by this authorJudith Landman-Parker
Pediatric Hematology and Oncology Department, Sorbonne University APHP, A.Trousseau Hospital, Paris, France
Search for more papers by this authorThierry Leblanc
Pediatric Hematology and Immunology Department, Robert-Debré Hospital and Université Paris-Cité Paris, Paris, France
Search for more papers by this authorNicolas Boissel
Adolescent and Young Adults Hematology Department, St Louis Hospital, Paris, France
Search for more papers by this authorAurélie Cabannes-Hamy
Hematology Department, Versailles Hospital, Le Chesnay, France
Search for more papers by this authorCorresponding Author
Lucille Lew-Derivry
Pediatric Hematology and Oncology Department, Sorbonne University APHP, A.Trousseau Hospital, Paris, France
Correspondence
Lucille Lew-Derivry, Pediatric Hematology and Oncology Department, Sorbonne University APHP, A.Trousseau Hospital, Paris, France.
Email: [email protected]
Search for more papers by this authorFlorian Chevillon
Adolescent and Young Adults Hematology Department, St Louis Hospital, Paris, France
Search for more papers by this authorPauline Brice
Hemato-Oncology Department, St Louis Hospital, Paris, France
Search for more papers by this authorCamille Bigenwald
Hematology Department, Gustave Roussy Institute, Villejuif, France
Search for more papers by this authorJudith Landman-Parker
Pediatric Hematology and Oncology Department, Sorbonne University APHP, A.Trousseau Hospital, Paris, France
Search for more papers by this authorThierry Leblanc
Pediatric Hematology and Immunology Department, Robert-Debré Hospital and Université Paris-Cité Paris, Paris, France
Search for more papers by this authorNicolas Boissel
Adolescent and Young Adults Hematology Department, St Louis Hospital, Paris, France
Search for more papers by this authorAurélie Cabannes-Hamy
Hematology Department, Versailles Hospital, Le Chesnay, France
Search for more papers by this authorSummary
Hodgkin lymphoma (HL) is one of the most common cancers in adolescents and young adults (AYA). Paediatric and adult therapeutic strategies diverge while sharing the common objective: maintaining optimal efficacy with less long-term toxicity. However, few studies have compared the outcome of AYA treated according to one or the other approaches. Among the 148 patients aged 15–25 years, treated at Saint-Louis Hospital for newly diagnosed HL between 2012 and 2018, 71 were treated according to an adult protocol and 77 were treated according to a paediatric one. The 5-year overall survival (OS) and progression-free survival (PFS) were, respectively, 100% and 85%, with no significant difference between treatment groups (85% in paediatric vs. 86% in adult, p = 0.7). Overall, the 5-year PFS was 100% for early favourable stages and 78% for advanced stages. A higher risk of short-term steroid and vincristine-related toxicities was observed in paediatric regimen, whereas a higher risk of late toxicities was expected in adult regimen, due to higher anthracyclines, procarbazine, bleomycin and radiotherapy exposure. These results confirm the excellent outcome of AYA patients with HL, whatever the treatment strategies. They justify a tailor-made therapeutic decision and highlight the importance of managing AYA patients in dedicated units with trained professionals.
Graphical Abstract
Hodgkin lymphoma (HL) is one of the most common cancers in adolescents and young adults (AYA) yet no treatment specifically tailored to this age group currently exists. This study compared 148 patients aged 15 to 25 treated at Saint-Louis Hospital between 2012 and 2018, using either pediatric or adult protocols. A higher risk of short-term steroid and vincristine-related toxicities was observed in pediatric regimen, whereas a higher risk of late toxicities was expected in adult regimen, due to higher anthracyclines, procarbazine, bleomycin and radiotherapy exposure. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 100% and 85%, respectively, with no significant difference between the two approaches. These findings emphasize the importance of personalized care in specialized units to optimize treatment outcomes while minimizing short- and long-term toxicities. [Correction added on 15 April 2025, after first online publication: The graphical abstract was corrected in this version.]
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
Data available on request.
Supporting Information
Filename | Description |
---|---|
bjh19985-sup-0001-DataS1.docxWord 2007 document , 58.5 KB |
Data S1. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022; 72: 7–33.
- 2Kelly KM, Friedberg JW. Classic Hodgkin lymphoma in adolescents and young adults. J Clin Oncol. 2023; 42: 653–664. https://doi.org/10.1200/JCO.23.01799
- 3Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021; 71: 7–33.
- 4Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, et al. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010; 28: 3680–3686.
- 5Engert A, Schiller P, Josting A, Herrmann R, Koch P, Sieber M, et al. Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's lymphoma study group. J Clin Oncol. 2003; 21: 3601–3608.
- 6Bonadonna G, Bonfante V, Viviani S, di Russo A, Villani F, Valagussa P. ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin's disease: long-term results. J Clin Oncol. 2004; 22: 2835–2841.
- 7Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, et al. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012; 366: 399–408. https://doi.org/10.1056/NEJMoa1111961
- 8Engert A, Plütschow A, Eich HT, Lohri A, Dörken B, Borchmann P, et al. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med. 2010; 363: 640–652.
- 9Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, et al. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007; 357: 1916–1927.
- 10Eich HT, Diehl V, Görgen H, Pabst T, Markova J, Debus J, et al. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin study group HD11 trial. J Clin Oncol. 2010; 28: 4199–4206.
- 11Dörffel W, Lüders H, Rühl U, Albrecht M, Marciniak H, Parwaresch R, et al. Preliminary results of the multicenter trial GPOH-HD 95 for the treatment of Hodgkin's disease in children and adolescents: analysis and outlook. Klin Padiatr. 2003; 215: 139–145.
- 12Schellong G, Pötter R, Brämswig J, Wagner W, Prott FJ, Dörffel W, et al. High cure rates and reduced long-term toxicity in pediatric Hodgkin's disease: the German-Austrian multicenter trial DAL-HD-90. The German-Austrian pediatric Hodgkin's disease study group. J Clin Oncol. 1999; 17: 3736–3744.
- 13Santarsieri A, Sturgess K, Brice P, Menne TF, Osborne W, Creasey T, et al. Procarbazine-free escalated Beacopdac in frontline therapy of advanced Hodgkin lymphoma reduces red cell transfusion requirements and may shorten time to menstrual period recovery compared to escalated Beacopp and appears to be as efficacious. Blood. 2019; 134: 1564.
- 14Boissel N, Auclerc MF, Lhéritier V, Perel Y, Thomas X, Leblanc T, et al. Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol. 2003; 21: 774–780.
- 15Mauz-Körholz C, Landman-Parker J, Balwierz W, Ammann RA, Anderson RA, Attarbaschi A, et al. Response-adapted omission of radiotherapy and comparison of consolidation chemotherapy in children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma (EuroNet-PHL-C1): a titration study with an open-label, embedded, multinational, non-inferiority, randomised controlled trial. Lancet Oncol. 2022; 23: 125–137.
- 16Eichenauer DA, Bredenfeld H, Haverkamp H, Müller H, Franklin J, Fuchs M, et al. Hodgkin's lymphoma in adolescents treated with adult protocols: a report from the German Hodgkin study group. J Clin Oncol. 2009; 27: 6079–6085.
- 17Gupta S, Baxter NN, Hodgson D, Punnett A, Sutradhar R, Pole JD, et al. Treatment patterns and outcomes in adolescents and young adults with Hodgkin lymphoma in pediatric versus adult centers: an IMPACT cohort study. Cancer Med. 2020; 9: 6933–6945.
- 18Henderson TO, Parsons SK, Wroblewski KE, Chen L, Hong F, Smith SM, et al. Outcomes in adolescents and young adults (AYA) with Hodgkin lymphoma (HL) treated on US cooperative group protocols: an adult intergroup (E2496) and Children's oncology group (COG AHOD 0031) comparative analysis. Cancer. 2018; 124: 136–144.
- 19Mottl AA, Fisher SG, Fisher RI, Constine LS, Friedberg JW. Adolescents with Hodgkin lymphoma treated on adult and pediatric protocols have distinct therapeutic outcome. Blood. 2004; 104: 312.
- 20Strongman H, Brown A, Smeeth L, Bhaskaran K. Body mass index and Hodgkin's lymphoma: UK population-based cohort study of 5.8 million individuals. Br J Cancer. 2019; 120: 768–770.
- 21Shanbhag S, Ambinder RF. Hodgkin lymphoma: a review and update on recent progress. CA Cancer J Clin. 2018; 68: 116–132.
- 22Casasnovas R-O, Bouabdallah R, Brice P, Lazarovici J, Ghesquieres H, Stamatoullas A, et al. Positron emission tomography–driven strategy in advanced Hodgkin lymphoma: prolonged follow-up of the AHL2011 phase III lymphoma study association study. J Clin Oncol. 2022; 40: 1091–1101.
- 23Federico M, Fortpied C, Stepanishyna Y, Gotti M, van der Maazen R, Cristinelli C, et al. Long-term follow-up of the response-adapted intergroup EORTC/LYSA/FIL H10 trial for localized Hodgkin lymphoma. J Clin Oncol. 2024; 42: 19–25.
- 24Fuchs M, Jacob AS, Kaul H, Kobe C, Kuhnert G, Pabst T, et al. Follow-up of the GHSG HD16 trial of PET-guided treatment in early-stage favorable Hodgkin lymphoma. Leukemia. 2024; 38: 160–167.
- 25Casasnovas R-O, Bouabdallah R, Brice P, Lazarovici J, Ghesquieres H, Stamatoullas A, et al. PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2019; 20: 202–215.
- 26Johnson P, Federico M, Kirkwood A, Fosså A, Berkahn L, Carella A, et al. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma. N Engl J Med. 2016; 374: 2419–2429.
- 27Fuchs M, Goergen H, Kobe C, Kuhnert G, Lohri A, Greil R, et al. Positron emission tomography-guided treatment in early-stage favorable Hodgkin lymphoma: final results of the international, randomized phase III HD16 trial by the German Hodgkin study group. J Clin Oncol. 2019; 37: 2835–2845.
- 28Borchmann P, Goergen H, Kobe C, Lohri A, Greil R, Eichenauer DA, et al. PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin study group. Lancet Lond Engl. 2017; 390: 2790–2802.
- 29De Re V, Repetto O, Mussolin L, Brisotto G, Elia C, Lopci E, et al. Promising drugs and treatment options for pediatric and adolescent patients with Hodgkin lymphoma. Front Cell Dev Biol. 2022; 10:965803.
- 30Follows AM, Santarsieri A. Minimising the toxicities of first line Hodgkin lymphoma treatment in the modern era. Cancer. 2022; 14: 5390.
- 31Castellino SM, Geiger AM, Mertens AC, Leisenring WM, Tooze JA, Goodman P, et al. Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the childhood cancer survivor study. Blood. 2011; 117: 1806–1816.
- 32Ehrhardt MJ, Flerlage JE, Armenian SH, Castellino SM, Hodgson DC, Hudson MM. Integration of pediatric Hodgkin lymphoma treatment and late effects guidelines: seeing the Forest beyond the trees. J Natl Compr Cancer Netw. 2021; 19: 755–764.
- 33Robison LL, Bhatia S. Late-effects among survivors of leukaemia and lymphoma during childhood and adolescence. Br J Haematol. 2003; 122: 345–359.
- 34van Leeuwen FE, Klokman WJ, Veer MB, Hagenbeek A, Krol ADG, Vetter UAO, et al. Long-term risk of second malignancy in survivors of Hodgkin's disease treated during adolescence or young adulthood. J Clin Oncol. 2000; 18: 487.
- 35O'Brien MM, Donaldson SS, Balise RR, Whittemore AS, Link MP. Second malignant neoplasms in survivors of pediatric Hodgkin's lymphoma treated with low-dose radiation and chemotherapy. J Clin Oncol. 2010; 28: 1232–1239.
- 36Schellong G, Riepenhausen M. Late effects after therapy of Hodgkin's disease: update 2003/04 on overwhelming post-splenectomy infections and secondary malignancies. Klin Padiatr. 2004; 216: 364–369.
- 37Schaapveld M, Aleman BMP, van Eggermond AM, Janus CPM, Krol ADG, van der Maazen RWM, et al. Second cancer risk up to 40 years after treatment for Hodgkin's lymphoma. N Engl J Med. 2015; 373: 2499–2511.
- 38Eichenauer DA, Thielen I, Haverkamp H, Franklin J, Behringer K, Halbsguth T, et al. Therapy-related acute myeloid leukemia and myelodysplastic syndromes in patients with Hodgkin lymphoma: a report from the German Hodgkin study group. Blood. 2014; 123: 1658–1664.
- 39Nanda R, Flampouri S, Mendenhall NP, Indelicato DJ, Jones LM, Seeram VK, et al. Pulmonary toxicity following proton therapy for thoracic lymphoma. Int J Radiat Oncol Biol Phys. 2017; 99: 494–497.
- 40Banfill K, Giuliani M, Aznar M, Franks K, McWilliam A, Schmitt M, et al. Cardiac toxicity of thoracic radiotherapy: existing evidence and future directions. J Thorac Oncol. 2021; 16: 216–227.
- 41Neppelenbroek SIM, Geurts YM, Aleman BMP, Lugtenburg PJ, Rademakers SE, de Weijer RJ, et al. Doxorubicin exposure and breast cancer risk in survivors of adolescent and adult Hodgkin lymphoma. J Clin Oncol. 2024; 42: 1903–1913. https://doi.org/10.1200/JCO.23.01386
- 42McGrady ME, Ketterl TG, Norris RE, Perentesis JP, Pettee D, Mara CA, et al. Barriers to medication adherence among adolescents and young adults with cancer. Pediatr Blood Cancer. 2023; 70:e30186.
- 43Bleyer A. The adolescent and young adult gap in cancer care and outcome. Curr Probl Pediatr Adolesc Health Care. 2005; 35: 182–217.
- 44Kahn JM, Pei Q, Friedman DL, Kaplan J, Keller FG, Hodgson D, et al. Survival by age in paediatric and adolescent patients with Hodgkin lymphoma: a retrospective pooled analysis of children's oncology group trials. Lancet Haematol. 2022; 9: e49–e57.
- 45Ansell SM, Radford J, Connors JM, Długosz-Danecka M, Kim WS, Gallamini A, et al. Overall survival with brentuximab Vedotin in stage III or IV Hodgkin's lymphoma. N Engl J Med. 2022; 387: 310–320.
- 46Borchmann P, Ferdinandus J, Schneider G, Moccia A, Greil R, Hertzberg M, et al. Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial. Lancet Lond Engl. 2024; 404: 341–352.
- 47Castellino SM, Pei Q, Parsons SK, Hodgson D, McCarten K, Horton T, et al. Brentuximab Vedotin with chemotherapy in pediatric high-risk Hodgkin's lymphoma. N Engl J Med. 2022; 387: 1649–1660.
- 48Herrera AF, LeBlanc M, Castellino SM, Li H, Rutherford SC, Evens AM, et al. Nivolumab+AVD in advanced-stage classic Hodgkin's lymphoma. N Engl J Med. 2024; 391: 1379–1389.