Abstract
Pediatric, adolescent, and young adult patients with relapsed or refractory Hodgkin lymphoma receive multimodal therapy, including autologous hematopoietic cell transplantation (AutoHCT). Despite aggressive therapy, historical outcomes for this patient population have been poor. This paper describes a single institutional experience utilizing AutoHCT in 74 patients treated from 1988–2015. Our results demonstrate significantly improved outcomes over time. Compared with patients treated in the earlier era (1988–2001), 5-year overall survival improved from 62.5 ± 9.6% to 91.8 ± 4.4% (p < 0.001) and event free survival improved from 41.7 ± 9.6% to 87.7 ± 5.3% (I < 0.001) for patients treated in a later era (2002–2015). Improvements in survival are multifactorial, including reductions in both relapse and nonrelapse mortality. Further investigation is needed to determine the role of AutoHCT in a modern treatment cohort that includes frequent use of targeted immunotherapies. In addition, as the use and availability of effective novel therapeutics increases for this patient population there may be an opportunity for the reduction of standard cytotoxic therapies, including in AutoHCT preparative regimens, thereby mitigating late effects.
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References
Terezakis SA, Metzger ML, Hodgson DC, Schwartz CL, Advani R, Flowers CR, et al. ACR appropriateness criteria pediatric Hodgkin Lymphoma. Pediatr Blood Cancer. 2014;61:1305–12.
Hoppe BS, Flampouri S, Zaiden R, Slayton W, Sandler E, Ozdemir S, et al. Involved-node proton therapy in combined modality therapy for Hodgkin Lymphoma: results of a phase 2 study. Int J Radiat Oncol Biol Phys. 2014;89:1053–9.
Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, et al. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin’s lymphoma—a report from the Children’s Oncology Group. J Clin Oncol. 2012;30:3174–80.
Mauz-Korholz C, Metzger ML, Kelly KM, Schwartz CL, Castellanos ME, Dieckmann K, et al. Pediatric Hodgkin Lymphoma. J Clin Oncol. 2015;33:2975–85.
Metzger ML, Hudson MM, Krasin MJ, Wu J, Kaste SC, Kun LE, et al. Initial response to salvage therapy determines prognosis in relapsed pediatric Hodgkin lymphoma patients. Cancer. 2010;116:4376–84.
Hudson MM, Donaldson SS. Treatment of pediatric Hodgkin’s lymphoma. Semin Hematol. 1999;36:313–23.
Friedmann AM, Wolfson JA, Hudson MM, Weinstein HJ, Link MP, Billett A, et al. Relapse after treatment of pediatric Hodgkin lymphoma: outcome and role of surveillance after end of therapy. Pediatr Blood Cancer. 2013;60:1458–63.
Schellong G, Dorffel W, Claviez A, Korholz D, Mann G, Scheel-Walter HG, et al. Salvage therapy of progressive and recurrent Hodgkin’s disease: results from a multicenter study of the pediatric DAL/GPOH-HD study group. J Clin Oncol. 2005;23:6181–9.
Brockelmann PJ, Zagadailov EA, Corman SL, Chirikov V, Johnson C, Macahilig C, et al. Brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma who are Ineligible for autologous stem cell transplant: a Germany and United Kingdom retrospective study. Eur J Haematol. 2017;99:553–8.
Metzger ML, Mauz-Korholz C. Epidemiology, outcome, targeted agents and immunotherapy in adolescent and young adult non-Hodgkin and Hodgkin lymphoma. Br J Haematol. 2019;185:1142–57.
von Keudell G, Younes A. Novel therapeutic agents for relapsed classical Hodgkin lymphoma. Br J Haematol. 2019;184:105–12.
Garfin PM, Link MP, Donaldson SS, Advani RH, Luna-Fineman S, Kharbanda S, et al. Improved outcomes after autologous bone marrow transplantation for children with relapsed or refractory Hodgkin lymphoma: twenty years experience at a single institution. Biol Blood Marrow Transpl. 2015;21:326–34.
Sumaili H, Al-Kofide A, Al-Seraihi A, Ayas M, Siddiqui K, El-Solh H, et al. Outcome of pediatric patients with lymphoma following stem cell transplant: a single institution report. Leuk Lymphoma. 2015;56:1327–34.
Akhtar S, Rauf SM, Elhassan TA, Maghfoor I. Outcome analysis of high-dose chemotherapy and autologous stem cell transplantation in adolescent and young adults with relapsed or refractory Hodgkin lymphoma. Ann Hematol. 2016;95:1521–35.
Satwani P, Ahn KW, Carreras J, Abdel-Azim H, Cairo MS, Cashen A, et al. A prognostic model predicting autologous transplantation outcomes in children, adolescents and young adults with Hodgkin lymphoma. Bone Marrow Transplant. 2015;50:1416–23.
Verdeguer A, Pardo N, Madero L, Martinez A, Bureo E, Fernandez JM, et al. Autologous stem cell transplantation for advanced Hodgkin’s disease in children. Spanish group for BMT in children (GETMON), Spain. Bone Marrow Transplant. 2000;25:31–4.
Baker KS, Gordon BG, Gross TG, Abromowitch MA, Lyden ER, Lynch JC, et al. Autologous hematopoietic stem-cell transplantation for relapsed or refractory Hodgkin’s disease in children and adolescents. J Clin Oncol. 1999;17:825–31.
Daw S, Wynn R, Wallace H. Management of relapsed and refractory classical Hodgkin lymphoma in children and adolescents. Br J Haematol. 2011;152:249–60.
Abdalla A, Hammad M, Hafez H, Zaghloul MS, Taha H, El-Hennawy G, et al. Outcome predictors of autologous hematopoietic stem cell transplantation in children with relapsed and refractory Hodgkin lymphoma: Single-center experience in a lower-middle-income country. Pediatr Transplant. 2019;23:e13531.
National Cancer Institute. Adolescents and Young Adults with Cancer. http://www.cancer.gov/types/aya.
Burns LJ, Daniels KA, McGlave PB, Miller WJ, Ramsay NK, Kersey JH, et al. Autologous stem cell transplantation for refractory and relapsed Hodgkin’s disease: factors predictive of prolonged survival. Bone Marrow Transplant. 1995;16:13–8.
Crump M, Smith AM, Brandwein J, Couture F, Sherret H, Sutton DM, et al. High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin’s disease: importance of disease status at transplant. J Clin Oncol. 1993;11:704–11.
Moskowitz CH, Walewski J, Nademanee A, Masszi T, Agura E, Holowiecki J, et al. Five-year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse. Blood. 2018;132:2639–42.
Ansell SM. Immunotherapy in Hodgkin Lymphoma: the road ahead. Trends Immunol. 2019;40:380–6.
Brockelmann PJ, Borchmann P, Engert A. Current and future immunotherapeutic approaches in Hodgkin lymphoma. Leuk Lymphoma. 2016;57:2014–24.
Dahi PB, Moskowitz CH, Giralt SA, Lazarus HM. Novel agents positively impact chemotherapy and transplantation in Hodgkin lymphoma. Expert Rev Hematol. 2019:12;255–64.
Flerlage JE, Metzger ML, Bhakta N. The management of Hodgkin lymphoma in adolescents and young adults: burden of disease or burden of choice? Blood. 2018;132:376–84.
Hui L, von Keudell G, Wang R, Zeidan AM, Gore SD, Ma X, et al. Cost-effectiveness analysis of consolidation with brentuximab vedotin for high-risk Hodgkin lymphoma after autologous stem cell transplantation. Cancer. 2017;123:3763–71.
Hodgson DC, Gilbert ES, Dores GM, Schonfeld SJ, Lynch CF, Storm H, et al. Long-term solid cancer risk among 5-year survivors of Hodgkin’s lymphoma. J Clin Oncol. 2007;25:1489–97.
Castellino 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;117:1806–16.
Armstrong GT, Chen Y, Yasui Y, Leisenring W, Gibson TM, Mertens AC, et al. Reduction in late mortality among 5-year survivors of childhood cancer. N Engl J Med. 2016;374:833–42.
Bhuller KS, Zhang Y, Li D, Sehn LH, Goddard K, McBride ML, et al. Late mortality, secondary malignancy and hospitalisation in teenage and young adult survivors of Hodgkin lymphoma: report of the Childhood/Adolescent/Young Adult Cancer Survivors Research Program and the BC Cancer Agency Centre for Lymphoid Cancer. Br J Haematol. 2016;172:757–68.
Pui CH, Campana D, Pei D, Bowman WP, Sandlund JT, Kaste SC, et al. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med. 2009;360:2730–41.
Ramos CA, Ballard B, Zhang H, Dakhova O, Gee AP, Mei Z, et al. Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes. J Clin Investig. 2017;127:3462–71.
Harker-Murray PD, Drachtman RA, Hodgson DC, Chauvenet AR, Kelly KM, Cole PD. Stratification of treatment intensity in relapsed pediatric Hodgkin lymphoma. Pediatr Blood Cancer. 2014;61:579–86.
Tinkle CL, Williams NL, Wu H, Wu J, Kaste SC, Shulkin BL, et al. Treatment patterns and disease outcomes for pediatric patients with refractory or recurrent Hodgkin lymphoma treated with curative-intent salvage radiotherapy. Radiother Oncol. 2019;134:89–95.
Khurana A, Armand P, Ansell SM. Checkpoint inhibition therapy as possible frontline therapy for Hodgkin lymphoma. Leuk Lymphoma. 2020:1–12. [Epub ahead of print].
Geoerger B, Kang HJ, Yalon-Oren M, Marshall LV, Vezina C, Pappo A, et al. Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumour or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2020;21:121–33.
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This work was supported in part by the American Lebanese Syrian Associated Charities (ALSAC).
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Talleur, A.C., Flerlage, J.E., Shook, D.R. et al. Autologous hematopoietic cell transplantation for the treatment of relapsed/refractory pediatric, adolescent, and young adult Hodgkin lymphoma: a single institutional experience. Bone Marrow Transplant 55, 1357–1366 (2020). https://doi.org/10.1038/s41409-020-0879-4
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DOI: https://doi.org/10.1038/s41409-020-0879-4
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