Download PDF
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2020; 41(04): 492-509
DOI: 10.4103/ijmpo.ijmpo_135_20
Review Article

Hodgkin Lymphoma in Children and Adolescents: Advances in Pathology, Diagnosis, and Treatment Strategies

Contributor(s):
Adil Abbas
1   Department of Pediatrics, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
2   Princess Nourah Oncology Centre, King Abdulaziz Medical City, Jeddah, Saudi Arabia
,
Hatim Almaghraby
3   Department of Pathology, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
4   Department of Laboratory Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia
› Author Affiliations Financial support and sponsorship Nil.
› Further Information
   Permissions and Reprints

Abstract

Strategies used for the treatment of children with Hodgkin lymphoma (HL) over the last four decades have resulted in excellent long-term survivals. However, the short- and long-term treatment-associated morbidities were high. In an attempt to reduce complications, the current treatment strategies apply initial risk stratification principles based on certain host and tumor risk factors to help assign patients to the appropriate risk group and tailor therapy based on response to chemotherapy (CTR). Radiotherapy (RT) was only given to certain groups of patients who show suboptimal response to CTR. Enrollment of patients in clinical trials allowed testing newer treatment strategies, which has improved the outcome significantly. High-dose CTR with stem cell support remains the mainstay of treatment for relapsed and refractory HL. Newer targeted medications are being increasingly used for the treatment of patients with relapsed and refractory HL, but results are variable. In this review report, we give extensive account about the pathophysiology, clinical presentation, histopathological diagnosis, modern investigation techniques, the most recent risk adapted treatment strategies, and the use and effect of novel medications. In addition, we discuss in details the short- and long-term therapy-related complications and future prospects in the management of HL.

Keywords

18Fluorodeoxyglucose–positron emission tomography scan - chemotherapy - Hodgkin lymphoma - pathological classification - radiotherapy - staging system


Publication History

Received: 05 April 2020

Accepted: 18 April 2020

Article published online:
17 May 2021

© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Longo DL, Armitage JO. Controversies in the treatment of early-stage Hodgkin's lymphoma. N Engl J Med 2015; 372: 1667-9
    CrossrefPubMedGoogle Scholar
  • 2 Surveillance, Epidemiology, and End Results (SEER) Program Data 2017. USA: National Cancer Institute (NCI). https://seer.cancer.gov/ Available from: [Last accessed on 2019 Sep 20]
    Google Scholar
  • 3 Medeiros LJ, Greiner TC. Hodgkin's disease. Cancer 1995; 75: 357-69
    CrossrefPubMedGoogle Scholar
  • 4 Schwartz CL. Special issues in pediatric Hodgkin's disease. Eur J Haematol Suppl 2005; 66: 55-62
    CrossrefPubMedGoogle Scholar
  • 5 Wiegner EA, Donaldson SS. Controversies in radiotherapy for pediatric Hodgkin's lymphoma. Expert Rev Anticancer Ther 2011; 11: 1357-66
    PubMedGoogle Scholar
  • 6 Mendenhall NP, Cantor AB, Williams JL, Ternberg JL, Weiner MA, Kung FH. et al. With modern imaging techniques, is staging laparotomy necessary in pediatric Hodgkin's diseases? A Pediatric Oncology Group study. J Clin Oncol 1993; 11: 2218-25
    CrossrefPubMedGoogle Scholar
  • 7 Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri S, Stein H. WHO Classification of tumors of hematopoietic and lymphoid tissue. International agency for Research on Cancer, Lyon. (4th ed.) 2008. Blood 2011; 117: 5019-32
    CrossrefPubMedGoogle Scholar
  • 8 Hansmann ML, Willenbrock K. WHO classification of Hodgkin's lymphoma and its molecular pathological relevance. Pathologe 2002; 23: 207-18
    CrossrefPubMedGoogle Scholar
  • 9 Huppmann AR, Nicolae A, Slack GW, Pittaluga S, Davies-Hill T, Ferry JA. et al. EBV may be expressed in the LP cells of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in both children and adults. Am J Surg Pathol 2014; 38: 316-24
    CrossrefPubMedGoogle Scholar
  • 10 Grewal R, Irimie A, Naidoo N, Mohamed N, Petrushev B, Chetty M. et al. Hodgkin's lymphoma and its association with EBV and HIV infection. Crit Rev Clin Lab Sci 2018; 55: 102-14
    CrossrefPubMedGoogle Scholar
  • 11 Jarrett RF. Risk factors for Hodgkin's lymphoma by EBV status and significance of detection of EBV genomes in serum of patients with EBV-associated Hodgkin's lymphoma. Leuk Lymphoma 2003; 44: S27-32 Suppl 3
    CrossrefPubMedGoogle Scholar
  • 12 Meyer RM. EBV DNA: A Hodgkin lymphoma biomarker?. Blood 2013; 121: 3541-2
    CrossrefPubMedGoogle Scholar
  • 13 Park JH, Yoon DH, Kim S, Park JS, Park CS, Sung H. et al. Pretreatment whole blood Epstein -Barr virus – DNA is a significant prognostic marker in patients with Hodgkin's lymphoma. Ann Hematol 2016; 95: 801-8
    CrossrefPubMedGoogle Scholar
  • 14 Kirkorian JG, Portlock CS, Mauch PM. Hodgkin's disease presenting below the diaphragm: A review. J Clin Oncol 1986; 4: 1551-62
    CrossrefPubMedGoogle Scholar
  • 15 Li ZM, Zhu YJ, Xia Y, Huang JJ, Jiang WQ. Clinical characteristics of the patients with Hodgkin's lymphoma involving extranodal sites. Chin J Cancer 2012; 31: 342-7
    CrossrefPubMedGoogle Scholar
  • 16 Hudson MM, Schwartz C, Constine LS. Treatment of pediatric Hodgkin's lymphoma. In: Weinstein HJ, Hudson MM, Link MP. editors Pediatric Lymphomas. First edition. Springer – Verlag Publishers; Berlin, Heidelberg, Germany: 2007: 423
    Google Scholar
  • 17 Peng Y, Qing AC, Cai J, Yue C, French SW, Qing X. Lymphoma of the liver: Clinicopathological features of 19 patients. Exp Mol Pathol 2016; 100: 276-80
    CrossrefPubMedGoogle Scholar
  • 18 Padhan RK, Das P. Shalimar. Primary hepatic lymphoma. Trop Gastroenterol 2015; 36: 14-20
    CrossrefPubMedGoogle Scholar
  • 19 Dich NH, Goodman ZD, Klein MA. Hepatic involvement in Hodgkin's disease. Clues to histologic diagnosis. Cancer 1989; 64: 2121-6
    CrossrefPubMedGoogle Scholar
  • 20 Binesh F, Halvani H, Taghipour S, Navabii H. Primary pulmonary classic Hodgkin's lymphoma. BMJ Case Rep. 2011:2011. pii: bcr0320113955
  • 21 Kolygin BA, Vesnin AG. Hodgkin's disease in children: Involvement of lung and pleura. Pediatr Radiol 1976; 5: 75-80
    CrossrefPubMedGoogle Scholar
  • 22 Ha-ou-Nou FZ, Benjilali L, Essaadouni L. Sacral pain as the initial symptom in primary Hodgkin's lymphoma of bone. J Cancer Res Ther 2013; 9: 511-3
    CrossrefPubMedGoogle Scholar
  • 23 Singh P, Bakhshi S. Osseous involvement in pediatric Hodgkin's lymphoma. Indian J Pediatr 2010; 77: 565-6
    CrossrefPubMedGoogle Scholar
  • 24 Martinez DL, Gujrati M, Geoffroy F, Tsung AJ. Isolated CNS Hodgkin's lymphoma: Implications for tissue diagnosis. CNS Oncol 2014; 3: 383-7
    CrossrefPubMedGoogle Scholar
  • 25 Gessi M, Kuchelmeister K, Kellner U, Ritter M, Morgner A, Urbach H. et al. Unusual clinico-pathological features in primary Hodgkin's lymphomas of the central nervous system. Acta Neurochir (Wien) 2013; 155: 19-24
    CrossrefPubMedGoogle Scholar
  • 26 van Blydenstein SA, Patel M, Philip V, Lakha A, Pather S, Westgarth-Taylor T. et al. Classical Hodgkin Lymphoma involving the central nervous system (brain) – An unusual presentation. Clin Case Rep 2014; 2: 88-92
    CrossrefPubMedGoogle Scholar
  • 27 Tassies D, Sierra J, Montserrat E, Martí R, Estrach T, Rozman C. Specific cutaneous involvement in Hodgkin's disease. Hematol Oncol 1992; 10: 75-9
    CrossrefPubMedGoogle Scholar
  • 28 Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M. Report of the committee on Hodgkin's disease staging classification. Cancer Res 1971; 31: 1860-1
    PubMedGoogle Scholar
  • 29 Afaq A, Fraioli F, Sidhu H, Wan S, Punwani S, Chen SH. et al. Comparison of PET/MRI with PET/CT in the evaluation of disease status in lymphoma. Clin Nucl Med 2017; 42: e1-7
    CrossrefPubMedGoogle Scholar
  • 30 Subocz E, Hałka J, Dziuk M. The role of FDG-PET in Hodgkin lymphoma. Contemp Oncol (Pozn) 2017; 21: 104-14
    PubMedGoogle Scholar
  • 31 Freed J, Kelly KM. Current approaches to the management of pediatric Hodgkin lymphoma. Paediatr Drugs 2010; 12: 85-98
    CrossrefPubMedGoogle Scholar
  • 32 Castellani MR, Cefalo G, Terenziani M, Aliberti G, Maccauro M, Alessi A. et al. Gallium scan in adolescents and children with Hodgkin's disease (HD). Treatment response assessment and prognostic value. Q J Nucl Med 2003; 47: 22-30
    PubMedGoogle Scholar
  • 33 Escobar GI, Lopez A, Rubio J, Perez-Callejo D, Barrigón DC, Alonso PT. et al. Clinical pretreatment risk factors and prediction of outcome using gallium 67 scintigraphy in patients with Hodgkin's lymphoma. Mol Clin Oncol 2016; 4: 93-9
    CrossrefPubMedGoogle Scholar
  • 34 Cole PD, McCarten KM, Drachtman RA, De Alarcon P, Chen L, Trippett TM. et al. Early FDG-PET-based response evaluation after treatment with gemcitabine and vinorelbine for refractory Hodgkin disease: A Children's Oncology Group Report. Pediatr Hematol Oncol 2010; 27: 650-7
    CrossrefPubMedGoogle Scholar
  • 35 Lin HM Teitell MA. Second malignancy after treatment of pediatric Hodgkin's lymphoma. J Pediatr Hematol Oncol 2005; 27: 28-36
    CrossrefPubMedGoogle Scholar
  • 36 Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med 1991; 324: 808-15
    CrossrefPubMedGoogle Scholar
  • 37 Marina VM, Greenwald CA, Fairclough DL, Thompson EI, Wilimas JA, Mackert PW. et al. Serial pulmonary function studies in children treated for newly diagnosed Hodgkin's disease with mantle radiotherapy plus cycles of cyclophosphamide, vincristine and procarbazine alternating with cycles of doxorubicin, bleomycin, vinblastine and dacarbazine. Cancer 1995; 75: 1706-11
    CrossrefPubMedGoogle Scholar
  • 38 Canellos GP. Can MOPP be replaced in the treatment of advanced Hodgkin's disease?. Semin Oncol 1990; 17: 2-6
    PubMedGoogle Scholar
  • 39 van den Berg H, Stuve W, Behrendt H. Treatment of Hodgkin's disease in children with alternating mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) courses without radiotherapy. Med Pediatr Oncol 1997; 29: 23-7
    CrossrefPubMedGoogle Scholar
  • 40 Hay AE, Meyer RM. Balancing risks and benefits of therapy for patients with favorable-risk limited-stage Hodgkin lymphoma: The role of ABVD chemotherapy alone. Hematol Oncol Clin North Am 2014; 28: 49-63
    CrossrefPubMedGoogle Scholar
  • 41 Probert JC, Parker BR, Kaplan HS. Growth retardation in children after megavoltage irradiation of the spine. Cancer 1973; 32: 634-9
    CrossrefPubMedGoogle Scholar
  • 42 Donaldson SS, Link MP. Combined modality treatment with low dose radiation and MOPP chemotherapy for children with Hodgkin's disease. J Clin Oncol 1987; 5: 742-9
    CrossrefPubMedGoogle Scholar
  • 43 Specht L. Prognostic factors in Hodgkin's disease. Semin Radiat Oncol 1996; 6: 146-61
    CrossrefPubMedGoogle Scholar
  • 44 Moccia AA, Donaldson J, Chhanabhai M, Hoskins PJ, Klasa RJ, Savage KJ. et al. International Prognostic Score in advanced-stage Hodgkin's lymphoma: Altered utility in the modern era. J Clin Oncol 2012; 30: 3383-8
    CrossrefPubMedGoogle Scholar
  • 45 Schwartz CL, Chen L, McCarten K, Wolden S, Constine LS, Hutchison RE. et al. Childhood Hodgkin's International Prognostic Score (CHIPS) Predicts eventfree survival in Hodgkin's Lymphoma: A Report from the Children's Oncology Group. Pediatr Blood Cancer 2017; 64: 1-18 DOI: 10.1002/pbc.26278.
    CrossrefPubMedGoogle Scholar
  • 46 Giulino-Roth L, Keller FG, Hodgson DC, Kelly KM. Current approaches in the management of low risk Hodgkin lymphoma in children and adolescents. Br J Haematol 2015; 169: 647-60
    CrossrefPubMedGoogle Scholar
  • 47 Dörffel W, Rühl U, Lüders H, Claviez A, Albrecht M, Bökkerink J. et al. Treatment of children and adolescents with Hodgkin lymphoma without radiotherapy for patients in complete remission after chemotherapy: Final results of the multinational trial GPOH-HD95. J Clin Oncol 2013; 31: 1562-8
    CrossrefPubMedGoogle Scholar
  • 48 Radford J, Illidge T, Counsell N, Hancock B, Pettengell R, Johnson P. et al. Results of a trial of PET-directed therapy for early – Stage Hodgkin's lymphoma. N Engl J Med 2015; 372: 1598-607
    CrossrefPubMedGoogle Scholar
  • 49* Donaldson SS, Link MP, Weinstein HJ, Rai SN. Final results of a prospective clinical trial with VAMP and low-dose involved-field radiation for children with low-risk Hodgkin's disease. J Clin Oncol 2007; 25: 332-7
    CrossrefPubMedGoogle Scholar
  • 50 Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ. et al. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: A Report from the Children's Oncology Group Study AHOD0031. J Clin Oncol 2014; 32: 3651-8
    CrossrefPubMedGoogle Scholar
  • 51 Hehn ST, Miller TP. What is the treatment of choice for advanced-stage Hodgkin's lymphoma: ABVD, Stanford V, or BEACOPP?. Curr Hematol Rep 2004; 3: 17-26
    PubMedGoogle Scholar
  • 52 Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V. et al. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med 2011; 365: 203-12
    CrossrefPubMedGoogle Scholar
  • 53 Kelly KM, Sposto R, Hutchinson R, Massey V, McCarten K, Perkins S. et al. BEACOPP chemotherapy is a highly effective regimen in children and adolescents with high-risk Hodgkin lymphoma: A report from the Children's Oncology Group. Blood 2011; 117: 2596-603
    CrossrefPubMedGoogle Scholar
  • 54 Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R. et al. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: The results of P9425. Blood 2009; 114: 2051-9
    CrossrefPubMedGoogle Scholar
  • 55 Savage KJ, Mottok A, Fanale M. Nodular lymphocyte-predominant Hodgkin lymphoma. Semin Hematol 2016; 53: 190-202
    CrossrefPubMedGoogle Scholar
  • 56 Gorde-Grosjean S, Guimard G, Lambilliotte A, Coulomb-Lhermine A, Montravers F, Landman-Parker J. Nodular lymphocyte-predominant Hodgkin lymphoma in children: Clinical course, biology, and management. Bull Cancer 2014; 101: 881-90
    PubMedGoogle Scholar
  • 57 van Grotel M, Lam KH, de Man R, Beishuizen A, Pieters R, van den Heuvel-Eibrink MM. High relapse rate in children with non-advanced nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL or nodular paragranuloma) treated with chemotherapy only. Leuk Lymphoma 2006; 47: 1504-10
    CrossrefPubMedGoogle Scholar
  • 58 Schlembach PJ, Wilder RB, Jones D, Ha CS, Fayad LE, Younes A, Hagemeister F. et al. Radiotherapy alone for lymphocyte-predominant Hodgkin's disease. Cancer J 2002; 8: 377-83
    CrossrefPubMedGoogle Scholar
  • 59 Claviez A, Sureda A, Schmitz N. Hematopoietic SCT for children and adolescents with relapsed and refractory Hodgkin's lymphoma. Bone Marrow Transplant 2008; 42 Suppl 2: S16-24
    CrossrefPubMedGoogle Scholar
  • 60 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
    CrossrefPubMedGoogle Scholar
  • 61 Devillier R, Coso D, Castagna L, Brenot Rossi I, Anastasia A, Chiti A. et al. Positron emission tomography scan response at the time of autologous transplant predicts outcome of patients with relapse/refractory Hodgkin's lymphoma. Haematologica 2012; 97: 1073-9
    CrossrefPubMedGoogle Scholar
  • 62 Cole PD, McCarten KM, Pei Q, Spira M, Metzger ML, Drachtman RA. et al. Brentuximab vedotin with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin's lymphoma (AHOD1221): A Children's Oncology Group, multicentre single-arm, phase 1-2 trial. Lancet Oncol 2018; 19: 1229-38
    CrossrefPubMedGoogle Scholar
  • 63 Younes A. Brentuximab vedotin for the treatment of patients with Hodgkin lymphoma. Hematol Oncol Clin North Am 2014; 28: 27-32
    CrossrefPubMedGoogle Scholar
  • 64 Bonthapally V, Wu E, Macalalad A, Yang H, Shonukan O, Liu Y. et al. Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma post-autologous transplant: Meta-analysis versus historical data. Curr Med Res Opin 2015; 31: 993-1001
    CrossrefPubMedGoogle Scholar
  • 65 Chen R, Palmer JM, Martin P, Tsai N, Kim Y, Chen BT. et al. Results of a multicenter phase II trial of brentuximab vedotin as second-line therapy before autologous transplantation in relapsed/refractory Hodgkin lymphoma. Biol Blood Marrow Transplant 2015; 21: 2136-40
    CrossrefPubMedGoogle Scholar
  • 66 Gallamini A, Barrington SF, Biggi A, Chauvie S, Kostakoglu L, Gregianin M. et al. The predictive role of interim positron emission tomography for Hodgkin lymphoma treatment outcome is confirmed using the interpretation criteria of the Deauville five-point scale. Haematologica 2014; 99: 1107-13
    CrossrefPubMedGoogle Scholar
  • 67 Adams HJ, Kwee TC. Prognostic value of pre-transplant FDG-PET in refractory/relapsed Hodgkin's lymphoma treated with autologous stem cell transplantation: Systematic review and meta-analysis. Ann Hematol 2016; 95: 695-706
    CrossrefPubMedGoogle Scholar
  • 68 Mauz-Körholz C, Metzger ML, Kelly KM. Pediatric Hodgkin lymphoma. J Clin Oncol 2015; 33: 2975-85
    CrossrefPubMedGoogle Scholar
  • 69 Voss SD, Chen L, Constine LS, Chauvenet A. Surveillance computed tomography imaging and detection of relapse in intermediate- and advanced-stage pediatric Hodgkin's lymphoma: A report from the Children's Oncology Group. J Clin Oncol 2012; 30: 2635-40
    CrossrefPubMedGoogle Scholar
  • 70 Ferreira AL, Matsubara LS, Matsubara BB. Anthracycline induced cardiotoxicity. Cardiovasc Hematol Agents Med Chem 2008; 6: 278-81
    CrossrefPubMedGoogle Scholar
  • 71 Larussi D, Indolfi P, Galderisi M, Bossone E. Cardiac toxicity after anthracycline chemotherapy in childhood. Herz 2000; 25: 676-88
    CrossrefPubMedGoogle Scholar
  • 72 Bijl JM, Roos MM, van Leeuwen-Segarceanu EM, Vos JM, Bos WW, Biesma DH. et al. Assessment of valvular disorders in survivors of Hodgkin's lymphoma treated by mediastinal radiotherapy±chemotherapy. Am J Cardiol 2016; 117: 691-6
    CrossrefPubMedGoogle Scholar
  • 73 Amini A, Murphy B, Cost CR, Garrington TP, Greffe BS, Liu AK. Cardiac mortality in children and adolescents with Hodgkin's lymphoma: A surveillance, epidemiology and end results analysis. J Adolesc Young Adult Oncol 2016; 5: 181-6
    CrossrefPubMedGoogle Scholar
  • 74 Bossi G, Cerveri I, Volpini E, Corsico A, Baio A, Corbella F, Klersy C. et al. Long-term pulmonary sequelae after treatment of childhood Hodgkin's disease. Ann Oncol 1997; 8 Suppl 1: 19-24
    CrossrefPubMedGoogle Scholar
  • 75 Hohl RJ, Schilsky RL. Nonmalignant complications of therapy for Hodgkin's disease. Hematol Oncol Clin North Am 1989; 3: 331-43
    CrossrefPubMedGoogle Scholar
  • 76 Van Dorp W, van Beek RD, Laven JS, Pieters R, de Muinck Keizer-Schrama SM, van den Heuvel-Eibrink MM. et al. Long-term endocrine side effects of childhood Hodgkin's lymphoma treatment: A review. Hum Reprod Update 2012; 18: 12-28
    CrossrefPubMedGoogle Scholar
  • 77 Demirkaya M, Sevinir B, Saǧlam H, Özkan L, Akacı O. Thyroid functions in long-term survivors of pediatric Hodgkin's lymphoma treated with chemotherapy and radiotherapy. J Clin Res Pediatr Endocrinol 2011; 3: 89-94
    CrossrefPubMedGoogle Scholar
  • 78 Krawczuk-Rybak M, Płonowski M, Solarz E, Leszczyńska E, Wojtkowska M, Wysocka J. Gonadal and thyroid function after treatment for Hodgkin's lymphoma in adolescents. Med Wieku Rozwoj 2008; 12: 1014-20 et al. 4 Pt 2
    PubMedGoogle Scholar
  • 79 De Bruin ML, Huisbrink J, Hauptmann M, Kuenen MA. et al. Treatment-related risk factors for premature menopause following Hodgkin lymphoma. Blood 2008; 111: 101-8
    CrossrefPubMedGoogle Scholar
  • 80 Bowers DC, McNeil DE, Liu Y, Yasui Y. Stroke as a late treatment effect of Hodgkin's disease: A report from the Childhood Cancer Survivor Study. J Clin Oncol 2005; 23: 6508-15
    CrossrefPubMedGoogle Scholar
  • 81 O'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: 1232-9
    CrossrefPubMedGoogle Scholar
  • 82 Dörffel W, Riepenhausen M, Lüders H, Brämswig J, Schellong G. Secondary malignancies following treatment for Hodgkin's lymphoma in childhood and adolescence. A cohort study with more than 30 years' follow-up. Dtsch Arztebl Int 2015; 112: 320-7
    PubMedGoogle Scholar
  • 83 Schellong G, Riepenhausen M, Ehlert K, Brämswig J, Schmutzler RK, Rhiem K. et al. Breast cancer in young women after treatment for Hodgkin's disease during childhood or adolescence – An observational study with up to 33-year follow-up. Dtsch Arztebl Int 2014; 111: 3-9
    PubMedGoogle Scholar
  • 84 Terezakis SA, Metzger ML, Hodgson DC, Schwartz CL, Advani R, Flowers CR, Hoppe BS. et al. ACR appropriateness criteria pediatric Hodgkin lymphoma. Pediatr Blood Cancer 2014; 61: 1305-12
    CrossrefPubMedGoogle Scholar
  • 85 Fernández KS, Schwartz CL, Chen L, Constine LS, Chauvenet A, de Alarcón PA. et al. Outcome of adolescents and young adults compared to children with Hodgkin lymphoma treated with response-based chemotherapy on pediatric protocols: A Children's Oncology Group report. Pediatr Blood Cancer 2017; 64 DOI: 10.1002/pbc.26681. Epub 2017 Jun 14
    CrossrefPubMedGoogle Scholar
  • 86 Maly J, Alinari L. Pembrolizumab in classical Hodgkin's lymphoma. Eur J Haematol 2016; 97: 219-27
    CrossrefPubMedGoogle Scholar
  • 87 Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P. et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol 2017; 35: 2125-32
    CrossrefPubMedGoogle Scholar