Hodgkin Disease

Abstract

Hodgkin disease is a malignancy of the lymphatic system, affecting predominantly young adults. Radio and chemotherapy have allowed long‐term cure in a large portion of patients. Unfortunately, 15–20% of patients can relapse and eventually die to this disease. CD30+ Reed–Sternberg cells represent the hallmark of this disease and they can be a variable, but usually very small portion of the cellular components of the affected lymph nodes. On the other hand, it is prominent the presence of a tumour microenvironment composed of nonmalignant B cells, T cells, granulocytes, eosinophils and stromal cells. It is thought that this microenvironment can influence the fate of the lymphoma cell growth and finally the clinical outcome of this disease. Recent therapeutic approaches such as chimeric anti‐CD30 antibody‐drug conjugates, chimeric antigen receptor T cells to the CD30 surface molecule and immune checkpoint inhibitors have given a new hope to treat patients with a relapsed/refractory disease.

Key Concept

  • Reed–Sternberg cells expressing CD30 membrane surface molecule are the main feature of the Hodgkin disease.
  • Reed–Sternberg cells induce a strong immunosuppressive tumour microenvironment.
  • Fluorodeoxyglucose (FDG) positron emission tomography (PET)–computerised tomography (CT) is essential to define the Hodgkin disease stage and the response to therapy.
  • Combination chemotherapy with ABVD or MOPP followed by X‐ray radiation is the standard treatment for Hodgkin disease.
  • 15–20% of Hodgkin disease patients do not respond to the combination chemotherapy and radiation or can relapse.
  • The salvage therapy consists of high‐dose combination chemotherapy followed by autologous or allogeneic hematopoietic stem‐cell transplantation.
  • Relapsed/refractory patients can be treated with anti‐CD30 drug‐conjugated antibodies or anti‐CD30 chimeric antigen receptor T cells or immune checkpoint inhibitors.
  • Immune checkpoint inhibitors are antibodies to molecules involved in the regulation of immune response.

Keywords: Hodgkin lymphoma; radio‐chemotherapy; immune checkpoint inhibitors; Reed–Sternberg cells; tumour microenvironment; CD30; CAR‐T cells; ADC; immunotherapy

Figure 1. A representative example of lymph node with HD. (a) Lymphoid follicle in the presence of a lymphadenitis. The typical structure of the follicle is conserved. (b) Altered organisation of a lymph node of a patient with NSCHL, (c) Reed–Sternberg (RS) cells (indicated by the white arrow) are the main feature of HD together with an evident inflammatory infiltrate. (d) In some instances, RS cells (indicated by the white arrow) can be isolated from HD lymph nodes and it is possible to culture them to study their functional characteristics. The morphology of cultured RS cells is similar to that of RS cells resident in the lymph node.
close

References

Advani RH, Hoppe RT, Baer D, et al. (2013) Efficacy of abbreviated Stanford V chemotherapy and involved‐field radiotherapy in early‐stage Hodgkin lymphoma: mature results of the G4 trial. Annual Oncology 24: 1044–1048.

Aleman BM, van den Belt‐Dusebout AW, De Bruin ML, et al. (2007) Late cardiotoxicity after treatment for Hodgkin lymphoma. Blood 109: 1878–1886.

Ansell SM, Lesokhin AM, Borrello I, et al. (2015) PD‐1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. New England Journal Medicine 372 (4): 311–319.

Armand P, Shipp MA, Ribrag V, et al. (2016) Programmed death‐1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. Journal of Clinical Oncology 34: 3733–3739.

Barrington SF, Mikhaeel NG, Kostakoglu L, et al. (2014) Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. Journal of Clinical Oncology 32: 3048–3058.

Barrington SF and Kluge R (2017) FDG PET for therapy monitoring in Hodgkin and non‐Hodgkin lymphomas. European Journal Nuclear Medicine Molecular Imaging 44: 97–110.

Baumeister SH, Freeman GJ, Dranoff G and Sharpe AH (2016) Coinhibitory pathways in immunotherapy for cancer. Annual Review Immunology 34: 539–573.

Biti GP, Cimino G, Cartoni C, et al. (1992) Extended‐field radiotherapy is superior to MOPP chemotherapy for the treatment of pathological‐stage I–IIA Hodgkin's disease: 8‐year update of an Italian prospective randomized study. Journal of Clinical Oncology 10: 378–382.

Bonadonna G, Zucali R, Monfardini S, De Lena M and Uslenghi C (1975) Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer 36: 252–259.

Butler TA (1981) Clinicopathologic study of 659 cases. Cancer 49: 1848–1858.

Carde P, Karrasch M, Fortpied C, et al. (2016) Eight cycles of ABVD versus four cycles of BEACOPPescalated plus four cycles of BEACOPPbaseline in stage III to IV, International Prognostic Score ≥ 3, high‐risk Hodgkin Lymphoma: first results of the phase III EORTC 20012 intergroup trial. Journal of Clinical Oncology 34: 2028–2036.

Cella D and Tross S (1986) Psychological adjustment to survival for Hodgkin's disease. Journal of Consulting and Clinical Psychology 54: 616–622.

Chen R, Zinzani PL, Fanale MA, et al. (2017) Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. Journal of Clinical Oncology 35: 2125–2132.

Constine L, Schwartz R, Savage D, et al. (1997) Cardiac function, perfusion and morbidity in irradiated long‐term survivors of Hodgkin's disease. International Journal of Radiation Oncology, Biology, Physics 39: 897–906.

Devita VT Jr, Serpick AA and Carbone PP (1970) Combination chemotherapy in the treatment of advanced Hodgkin's disease. Annals of Internal Medicine 73: 881–895.

El‐Galaly TC, d'Amore F, Mylam KJ, et al. (2012) Routine bone marrow biopsy has little or no therapeutic consequence for positron emission tomography/computed tomography‐staged treatment‐naive patients with Hodgkin lymphoma. Journal of Clinical Oncology 30: 4508–4514.

Engert A, Plutschow A, Eich HT, et al. (2010) Reduced treatment intensity in patients with early‐stage Hodgkin's lymphoma. The New England Journal of Medicine 363: 640–652.

Etter JL, Cannioto R, Soh KT, et al. (2018) Lifetime physical inactivity is associated with increased risk for Hodgkin and non‐Hodgkin lymphoma: a case‐control study. Leukemia Research 69: 7–11.

Evens AM and Kostakoglu L (2014) The role of FDG‐PET in defining prognosis of Hodgkin lymphoma for early‐stage disease. Blood 124: 3356–3364. Erratum in: (2015) Blood 125: 2450.

Gobbi PG, Levis A, Chisesi T, et al. (2005) Intergruppo Italiano LinfomiABVD versus modified Stanford V versus MOPPEBVCAD with optional and limited radiotherapy in intermediate‐ and advanced‐stage Hodgkin's lymphoma: final results of a multicenter randomized trial by the Intergruppo Italiano Linfomi. Journal of Clinical Oncology 23: 9198–9207.

Gordon LI, Hong F, Fisher RI, et al. (2013) Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced‐stage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). Journal of Clinical Oncology 31: 684–691.

Green MR, Monti S, Rodig SJ, et al. (2010) Integrative analysis reveals selective 9p24.1 amplification, increased PD‐1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B‐cell lymphoma. Blood 116: 3268–3277.

Grover NS and Savoldo B (2019) Challenges of driving CD30‐directed CAR‐T cells to the clinic. BMC Cancer 19: 203.

Gunawardana J, Chan FC, Telenius A, et al. (2014) Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma. Nature Genetics 46: 329–335.

Hancock S, Tucker M and Hoppe R (1993) Breast cancer after treatment of Hodgkin's disease. Journal of the National Cancer Institute 85: 25–31.

Harris NL, Jaffe ES, Diebold J, et al. (1999) World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the clinical advisory committee meeting – Airlie House, Virginia, November 1997. Journal of Clinical Oncology 17: 3835–3849.

Hodgkin T (1832) On some morbid appearances of the absorbent glands and spleen. Medico‐Chirurgical Transactions 17: 68–114.

Jacobs EM, Peters FC, Luce JK, et al. (1968) Mechlorethaminehcl and cyclophosphamide in the treatment of Hodgkin's disease and the lymphomas. JAMA: The Journal of the American Medical Association 203: 392–398.

van Leeuwen F, Klokman W, Stovall M, et al. (1995) Roles of radiotherapy and smoking in lung cancer following Hodgkin's disease. Journal of the National Cancer Institute 87: 1530–1537.

Lister TA, Crowther D, Sutcliffe SB, et al. (1989) Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. Journal of Clinical Oncology 7: 1630–1636.

Loeffler M, Brosteanu O, Hasenclever D, et al. (1998) Meta‐analysis of chemotherapy versus combined modality therapy trials in Hodgkin's disease. Journal of Clinical Oncology 16: 818–829.

Longo DL, Glatstein E, Duffey PL, et al. (1991) Radiation therapy versus combination chemotherapy in the treatment of early‐stage Hodgkin's disease: 7‐year results of a prospective randomized trial. Journal of Clinical Oncology 9: 906–917.

Mehra N, Ganesan P, Radhakrishnan V, et al. (2018) Effectiveness of end of therapy PET based deauville scoring in predicting outcomes in Hodgkin's lymphoma: a real‐world experience. Blood 132: 5921.

Merli F, Luminari S, Gobbi PG, et al. (2016) Long‐term results of the HD2000 trial comparing ABVD versus BEACOPP versus COPP‐EBV‐CAD in untreated patients with advanced Hodgkin lymphoma: a study by Fondazione Italiana Linfomi. Journal of Clinical Oncology 34: 1175–1181.

Nadali G, Vinante F, Ambrosetti A, et al. (1994) Serum levels of soluble CD30 are elevated in the majority of untreated patients with Hodgkin's disease and correlate with clinical features and prognosis. Journal of Clinical Oncology 12: 793–797.

Nimwegen FAV, Schaapveld M, Cutter DJ, et al. (2016) Radiation dose‐response relationship for risk of coronary heart disease in survivors of Hodgkin lymphoma. Journal of Clinical Oncology 34: 235–243.

Ramos CA, Ballard B, Zhang H, et al. (2017) Clinical and immunological responses after CD30‐specific chimeric antigen receptor‐redirected lymphocytes. Journal of Clinical Investigation 127: 3462–3471.

Shanbhag S and Ambinder RF (2018) Hodgkin lymphoma: a review and update on recent progress. CA: A Cancer Journal for Clinicans 68: 116–132.

Specht L, Gray K, Clarke M, et al. (1998) Influence of more extensive radiotherapy and adjuvant chemotherapy on long‐term outcome of early‐stage Hodgkin's disease: a metaanalysis of 23 randomized trials involving 3888 patients. Journal of Clinical Oncology 16: 830–843.

Tosetti F, Venè R, Camodeca C, et al. (2018) Specific ADAM10 inhibitors localize in exosome‐like vesicles released by Hodgkin lymphoma and stromal cells and prevent sheddase activity carried to bystander cells. Oncoimmunology 7 (5): e1421889.

Tubiana M, Henry‐Amar M, Carde P, et al. (1989) Toward comprehensive management tailored to prognostic factors of patients with clinical stages of I and II in Hodgkin's disease. The EORTC lymphoma group controlled clinical trials: 1964–1987. Blood 73: 47–56.

Vardhana S and Younes A (2016) The immune microenvironment in Hodgkin lymphoma: T cells, B cells, and immune checkpoints. Haematologica 101: 794–802.

Vassilakopoulos TP, Chatzidimitriou C, Asimakopoulos JV, et al. (2019) Immunotherapy in Hodgkin lymphoma: present status and future strategies. Cancers (Basel) 11 (8): pii: E1071.

Vaughan Hudson B, Vaughan Hudson G, Linch D, et al. (1994) Late mortality in young British National lymphoma investigation patients cured of Hodgkin's disease. Annals of Oncology, 5: 565–566.

Viviani S, Zinzani PL, Rambaldi A, et al. (2011) ABVD versus BEACOPP for Hodgkin's lymphoma when high‐dose salvage is planned. New England Journal of Medicine 365: 203–212.

Weniger MA, Melzner I, Menz CK, et al. (2006) Mutations of the tumor suppressor gene SOCS‐1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho‐STAT5 accumulation. Oncogene 25: 2679–2684.15.

Wu T, Mann R, Charache P, et al. (1990) Detection of epstein–barr virus messenger RNA in Reed–Sternberg cells of Hodgkin's disease. International Journal of Cancer 46: 801–804.

Yahalom J, Petrek J, Biddinger P, et al. (1992) Breast cancer in patients irradiated for Hodgkin's disease: a clinical and pathological analysis of 45 events in 37 patients. Journal of Clinical Oncology 10: 1674–1681.

Younes A, Santoro A, Shipp M, et al. (2016) Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem‐cell transplantation and brentuximab vedotin: a multicentre, multicohort, single‐arm phase 2 trial. Lancet Oncology 17: 1283–1294.

Zocchi MR, Catellani S, Canevali P, et al. (2012) High ERp5/ADAM10 expression in lymph node microenvironment and impaired NKG2D ligands recognition in Hodgkin lymphomas. Blood 119 (6): 1479–1489. DOI: 10.1182/blood-2011-07-370841.

Further Reading

Burton DR, Roitt IV, Delves PJ and Martin SJ (2016) Roitt's Essential Immunology. John Wiley and Sons Inc.: New York.

Devita VT, Mauch PM and Harris NL (1997) Hodgkin's disease. In: DeVita VT et al. (eds) Cancer: Principle and Practice of Oncology. Lippincott Williams and Wilkins: London.

Jaffe E (1999) Hodgkin's lymphoma. Seminars in Hematology 36 (3): 220–323.

Mauch PM, Armitage JO, Diehl V, et al. (1999) Hodgkin's Disease. Lippincott Williams and Wilkins: London.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Poggi, Alessandro(Feb 2020) Hodgkin Disease. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002170.pub2]