Hodgkin Lymphoma: Revisited

  • Brig Tathagata Chatterjee
  • Ankur Ahuja


Hodgkin lymphoma (HL), which in the past was called Hodgkin disease, has always been one of the front runners of research in lymphomas. It usually arises from germinal centre or post-germinal centre B cells. Composition of HL is commonly defined as having predominantly inflammatory cells having minor population of neoplastic cells which were named as Reed–Sternberg cells.


Hodgkin lymphoma EBV Pathophysiology of Hodgkin lymphoma RS cells PET/CT in HL EBV 


  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Ries LA, Kosary CL, Hankey BF, et al., editors. SEER cancer statistics review: 1973-1994, NIH publ no. 97-2 789. Bethesda: National Cancer Institute; 1997.Google Scholar
  3. 3.
    Correa P, O’Conor GT. Epidemiologic patterns of Hodgkin’s disease. Int J Cancer. 1971;8:192.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Correa P, O’Conor GT. Geographic pathology of lymphoreticular tumours: summary of survey from the geographic pathology committee of the international union against cancer. J Natl Cancer Inst. 1973;50:1609.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Gutensohn N, Cole P. Childhood social environment and Hodgkin’s disease. N Engl J Med. 1981;304:135.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Alexander FE, Jarrett RF, Lawrence D, et al. Risk factors for Hodgkin’s disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents. Br J Cancer. 2000;82:1117.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Chang KL, Albújar PF, Chen YY, et al. High prevalence of Epstein-Barr virus in the Reed-Sternberg cells of Hodgkin’s disease occurring in Peru. Blood. 1993;81:496.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Hjalgrim H, Askling J, Rostgaard K, et al. Characteristics of Hodgkin’s lymphoma after infectious mononucleosis. N Engl J Med. 2003;349:1324.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Tinguely M, Vonlanthen R, Müller E, et al. Hodgkin’s disease-like lymphoproliferative disorders in patients with different underlying immunodeficiency states. Mod Pathol. 1998;11:307.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Carbone A, Gloghini A, Larocca LM, et al. Human immunodeficiency virus-associated Hodgkin’s disease derives from post-germinal center B cells. Blood. 1999;93:2319.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Levine AM. HIV-associated Hodgkin’s disease. Biologic and clinical aspects. Hematol Oncol Clin North Am. 1996;10:1135.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Weiss LM, Chen YY, Liu XF, Shibata D. Epstein-Barr virus and Hodgkin’s disease. A correlative in situ hybridization and polymerase chain reaction study. Am J Pathol. 1991;139:1259.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Gledhill S, Gallagher A, Jones DB, et al. Viral involvement in Hodgkin’s disease: detection of clonal type A Epstein-Barr virus genomes in tumour samples. Br J Cancer. 1991;64:227.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Gahn TA, Schildkraut CL. The Epstein-Barr virus origin of plasmid replication, oriP, contains both the initiation and termination sites of DNA replication. Cell. 1989;58:527.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Kilger E, Kieser A, Baumann M, Hammerschmidt W. Epstein-Barr virus-mediated B-cell proliferation is dependent upon latent membrane protein 1, which simulates an activated CD40 receptor. EMBO J. 1998;17:1700.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Jarrett RF, MacKenzie J. Epstein-Barr virus and other candidate viruses in the pathogenesis of Hodgkin’s disease. Semin Hematol. 1999;36:260.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Sylla BS, Hung SC, Davidson DM, et al. Epstein-Barr virus-transforming protein latent infection membrane protein 1 activates transcription factor NF-kappaB through a pathway that includes the NF-kappaB-inducing kinase and the IkappaB kinases IKKalpha and IKKbeta. Proc Natl Acad Sci U S A. 1998;95:10106.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Cader FZ, Vockerodt M, Bose S, et al. The EBV oncogene LMP1 protects lymphoma cells from cell death through the collagen-mediated activation of DDR1. Blood. 2013;122:4237.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Mancao C, Hammerschmidt W. Epstein-Barr virus latent membrane protein 2A is a B-cell receptor mimic and essential for B-cell survival. Blood. 2007;110:3715.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Rengstl B, Newrzela S, Heinrich T, et al. Incomplete cytokinesis and re-fusion of small mononucleated Hodgkin cells lead to giant multinucleated Reed-Sternberg cells. Proc Natl Acad Sci U S A. 2013;110:20729.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Xavier de Carvalho A, Maiato H, Maia AF, et al. Reed-Sternberg cells form by abscission failure in the presence of functional Aurora B kinase. PLoS One. 2015;10:e0124629.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Tzankov A, Zimpfer A, Pehrs AC, et al. Expression of B-cell markers in classical Hodgkin lymphoma: a tissue microarray analysis of 330 cases. Mod Pathol. 2003;16:1141.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Kadin ME, Muramoto L, Said J. Expression of T-cell antigens on Reed-Sternberg cells in a subset of patients with nodular sclerosing and mixed cellularity Hodgkin’s disease. Am J Pathol. 1988;130:345.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Liso A, Capello D, Marafioti T, et al. Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte predominant and classic Hodgkin lymphoma. Blood. 2006;108:1013.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Marafioti T, Hummel M, Foss HD, et al. Hodgkin and Reed-Sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription. Blood. 2000;95:1443.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Kanzler H, Küppers R, Hansmann ML, Rajewsky K. Hodgkin and Reed-Sternberg cells in Hodgkin’s disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells. J Exp Med. 1996;184:1495.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Theil J, Laumen H, Marafioti T, et al. Defective octamer-dependent transcription is responsible for silenced immunoglobulin transcription in Reed-Sternberg cells. Blood. 2001;97:3191.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Stein H, Marafioti T, Foss HD, et al. Down-regulation of BOB.1/OBF.1 and Oct2 in classical Hodgkin disease but not in lymphocyte predominant Hodgkin disease correlates with immunoglobulin transcription. Blood. 2001;97:496.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Jundt F, Kley K, Anagnostopoulos I, et al. Loss of PU.1 expression is associated with defective immunoglobulin transcription in Hodgkin and Reed-Sternberg cells of classical Hodgkin disease. Blood. 2002;99:3060.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Ushmorov A, Ritz O, Hummel M, et al. Epigenetic silencing of the immunoglobulin heavy-chain gene in classical Hodgkin lymphoma-derived cell lines contributes to the loss of immunoglobulin expression. Blood. 2004;104:3326.PubMedCrossRefGoogle Scholar
  31. 31.
    Marafioti T, Pozzobon M, Hansmann ML, et al. Expression of intracellular signaling molecules in classical and lymphocyte predominance Hodgkin disease. Blood. 2004;103:188.PubMedCrossRefGoogle Scholar
  32. 32.
    Ushmorov A, Leithäuser F, Sakk O, et al. Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma. Blood. 2006;107:2493.PubMedCrossRefGoogle Scholar
  33. 33.
    Mathas S, Janz M, Hummel F, et al. Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphoma. Nat Immunol. 2006;7:207.PubMedCrossRefGoogle Scholar
  34. 34.
    Renné C, Martin-Subero JI, Eickernjäger M, et al. Aberrant expression of ID2, a suppressor of B-cell specific gene expression, in Hodgkin’s lymphoma. Am J Pathol. 2006;169:655.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Scheeren FA, Diehl SA, Smit LA, et al. IL-21 is expressed in Hodgkin lymphoma and activates STAT5: evidence that activated STAT5 is required for Hodgkin lymphomagenesis. Blood. 2008;111:4706.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Gilmore TD, Kalaitzidis D, Liang MC, Starczynowski DT. The c-Rel transcription factor and B-cell proliferation: a deal with the devil. Oncogene. 2004;23:2275.PubMedCrossRefGoogle Scholar
  37. 37.
    Horie R, Watanabe T, Morishita Y, et al. Ligand-independent signaling by overexpressed CD30 drives NFkappaB activation in Hodgkin-Reed-Sternberg cells. Oncogene. 2002;21:2493.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Horie R, Watanabe T, Ito K, et al. Cytoplasmic aggregation of TRAF2 and TRAF5 proteins in the Hodgkin- Reed-Sternberg cells. Am J Pathol. 2002;160:1647.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Buri C, Körner M, Schärli P, et al. CC chemokines and the receptors CCR3 and CCR5 are differentially expressed in the nonneoplastic leukocytic infiltrates of Hodgkin disease. Blood. 2001;97:1543.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Ghosh S, May MJ, Kopp EB. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998;16:225.PubMedCrossRefGoogle Scholar
  41. 41.
    Wu M, Lee H, Bellas RE, et al. Inhibition of NF-kappaB/Rel induces apoptosis of murine B cells. EMBO J. 1996;15:4682.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Takeda K, Kamanaka M, Tanaka T, et al. Impaired IL-13-mediated functions of macrophages in STAT6- deficient mice. J Immunol. 1996;157:3220.PubMedGoogle Scholar
  43. 43.
    Skinnider BF, Elia AJ, Gascoyne RD, et al. Signal transducer and activator of transcription 6 is frequently activated in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. Blood. 2002;99:618.PubMedCrossRefGoogle Scholar
  44. 44.
    Kreher S, Bouhlel MA, Cauchy P, et al. Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma. Proc Natl Acad Sci U S A. 2014;111:E4513.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Fhu CW, Graham AM, Yap CT, et al. Reed-Sternberg cell-derived lymphotoxin-α activates endothelial cells to enhance T-cell recruitment in classical Hodgkin lymphoma. Blood. 2014;124:2973.PubMedCrossRefGoogle Scholar
  46. 46.
    Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375–90.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Mauch PM, Kalish LA, Kadin M, et al. Patterns of presentation of Hodgkin disease. Implications for etiology and pathogenesis. Cancer. 1993;71:2062.PubMedCrossRefGoogle Scholar
  48. 48.
    Kaplan HS. Hodgkin's disease. 2nd ed. Cambridge: Harvard University Press; 1980.Google Scholar
  49. 49.
    Good GR, DiNubile MJ. Images in clinical medicine. Cyclic fever in Hodgkin’s disease (Pel-Ebstein fever). N Engl J Med. 1995;332:436.PubMedCrossRefGoogle Scholar
  50. 50.
    Gobbi PG, Cavalli C, Gendarini A, et al. Reevaluation of prognostic significance of symptoms in Hodgkin’s disease. Cancer. 1985;56:2874.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Atkinson K, Austin DE, McElwain TJ, Peckham MJ. Alcohol pain in Hodgkin’s disease. Cancer. 1976;37:895.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Cavalli F. Rare syndromes in Hodgkin’s disease. Ann Oncol. 1998;9(Suppl 5):S109.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Lucker GP, Steijlen PM. Acrokeratosis paraneoplastica (Bazex syndrome) occurring with acquired ichthyosis in Hodgkin’s disease. Br J Dermatol. 1995;133:322.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Perifanis V, Sfikas G, Tziomalos K, et al. Skin involvement in Hodgkin’s disease. Cancer Investig. 2006;24:401.CrossRefGoogle Scholar
  55. 55.
    Dabbs DJ, Striker LM, Mignon F, Striker G. Glomerular lesions in lymphomas and leukemias. Am J Med. 1986;80:63.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 15-1983. A 24-year-old man with cervical lymphadenopathy and the nephrotic syndrome. N Engl J Med. 1983;308:888.CrossRefGoogle Scholar
  57. 57.
    Seymour JF, Gagel RF. Calcitriol: the major humoral mediator of hypercalcemia in Hodgkin’s disease and non-Hodgkin’s lymphomas. Blood. 1993;82:1383.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Rieke JW, Donaldson SS, Horning SJ. Hypercalcemia and vitamin D metabolism in Hodgkin’s disease. Is there an underlying immunoregulatory relationship? Cancer. 1989;63:1700.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Di Biagio E, Sánchez-Borges M, Desenne JJ, et al. Eosinophilia in Hodgkin’s disease: a role for interleukin 5. Int Arch Allergy Immunol. 1996;110:244.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Teruya-Feldstein J, Jaffe ES, Burd PR, et al. Differential chemokine expression in tissues involved by Hodgkin’s disease: direct correlation of eotaxin expression and tissue eosinophilia. Blood. 1999;93:2463.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Peters MV, Alison RE, Bush RS. Natural history of Hodgkin’s disease as related to staging. Cancer. 1966;19:308.CrossRefGoogle Scholar
  62. 62.
    Kaplan HS. The radical radiotherapy of regionally localized Hodgkin’s disease. Radiology. 1962;78:553.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Rosenberg SA, Kaplan HS. Evidence for an orderly progression in the spread of Hodgkin’s disease. Cancer Res. 1966;26:1225.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Klimm B, Franklin J, Stein H, et al. Lymphocyte-depleted classical Hodgkin’s lymphoma: a comprehensive analysis from the German Hodgkin study group. J Clin Oncol. 2011;29:3914.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    NCCN guidelines version 2; 2016.Google Scholar
  66. 66.
    Gaulard P, Jaffe E, Krenacs L, Macon WR. Hepatosplenic T-cell lymphoma. In: Swerdlow SH, et al., editors. WHO classification of tumours of hematopoietic and lymphoid tissues. Lyon: IARC; 2008. p. 292–3.Google Scholar
  67. 67.
    Martelli M, Ferreri AJ, Johnson P. Primary mediastinal large B cell lymphoma. Crit Rev Oncol Hematol. 2008;68(3):256–63.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Barrington SF, Mikhaael NG, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of International conference on Malignant lymphoma Imaging work group. J Clin Oncol. 2014;32(27):3048–58.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Carbone PP, Kaplan HS, Musshoff K, et al. Report of the Committee on Hodgkin’s Disease Staging Classification. Cancer Res. 1971;31:1860.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Lister TA, Crowther D, Sutcliffe SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J Clin Oncol. 1989;7:1630.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Barrington SF, Mikhaeel NG. When should FDG-PET be used in the modern management of lymphoma? Br J Haematol. 2014;164:315.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Hutchings M, Loft A, Hansen M, et al. Position emission tomography with or without computed tomography in the primary staging of Hodgkin’s lymphoma. Haematologica. 2006;91:482.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Naumann R, Beuthien-Baumann B, Reiss A, et al. Substantial impact of FDG PET imaging on the therapy decision in patients with early-stage Hodgkin’s lymphoma. Br J Cancer. 2004;90:620.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Barrington SF, Kirkwood AA, Franceschetto A, et al. PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study. Blood. 2016;127:1531.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Advani RH, Horning SJ. Treatment of early-stage Hodgkin’s disease. Semin Hematol. 1999;36:270.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Ng AK, Weeks JC, Mauch PM, Kuntz KM. Decision analysis on alternative treatment strategies for favorable-prognosis, early-stage Hodgkin’s disease. J Clin Oncol. 1999;17:3577.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Moccia AA, Donaldson J, Chhanabhai M, Hoskins PJ, Klasa RJ, Savage KJ, Shenkier TN, Slack GW, Skinnider B, Gascoyne RD, Connors JM, Sehn LH. International Prognostic Score in advanced-stage Hodgkin’s lymphoma: altered utility in the modern era. J Clin Oncol. 2012;30(27):3383. Epub 2012 Aug 6.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Stein RS. Hodgkin’s disease. In: Lee GR, Foerester J, Lukens J, editors. Wintrobe’s clinical hematology. 10th ed. Baltimore: Williams and Wilkins; 1999. p. 2530–71.Google Scholar
  80. 80.
    Guermazi A, Brice P, de Kerviler EE, Fermé C, Hennequin C, Meignin V, et al. Extranodal Hodgkin disease: spectrum of disease. Radiographics. 2001;21:161–79.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Eustace S, O’Regan R, Graham D, Carney D. Primary multifocal skeletal Hodgkin’s disease confined to bone. Skelet Radiol. 1995;24:61–3.CrossRefGoogle Scholar
  82. 82.
    Fried G, Ben Arieh Y, Haim N, Dale J, Stein M. Primary Hodgkin’s disease of the bone. Med Pediatr Oncol. 1995;24:204–7.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Munker R, Harenclever D, Brosteanu O. Bone marrow involvement in Hodgkin’s disease: an analysis of 135 consecutive cases. German Hodgkin’s lymphoma study group. J Clin Oncol. 1996;14:682–3.CrossRefGoogle Scholar
  84. 84.
    Ostrowski ML, Inwards CY, Strickler JG, Witzig TE, Wenger DE, Unni KK. Osseous Hodgkin disease. Cancer. 1999;85:1166–78.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Hasenclever D, Diehl V. A prognostic score for advanced disease—international prognostic factors on advanced Hodgkin disease. NEJM. 1998;339:1506–14.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Ansell SM. Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016;91(4):434–42.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Hutchings M, Loft A, Hansen M, et al. FDGPET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood. 2006;107:52–9.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Gallamini A, Hutchings M, Rigacci L, et al. Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin’s lymphoma: a report from a joint Italian-Danish study. J Clin Oncol. 2007;25:3746–52.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Horning S. Hodgkin’s disease. In: Kaye S, editor. Textbook of medical oncology. 2nd ed. London: Martin Dunitz Publishers; 2000. p. 461–74.Google Scholar
  90. 90.
    Diehl V, Mauch PM, Harris NL. Hodgkin’s disease. In: De Vita VT, Hellman S, Rosenberg SA, editors. Principles and practice of oncology, vol. 2. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 2339–86.Google Scholar
  91. 91.
    Longo DL, Duffey PL, Young RC, et al. Conventional- dose salvage combination chemotherapy in patients relapsing with Hodgkin’s disease after combination chemotherapy: the low probability for cure. J Clin Oncol. 1992;10:210–8.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Bonfante V, Santoro A, Viviani S, et al. Outcome of patients with Hodgkin’s disease failing after primary MOPP-ABVD. J Clin Oncol. 1997;15:528–34.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Andre M, Henry-Amar M, Pico JL, et al. Comparison of high-dose therapy and autologous stem-cell transplantation with conventional therapy for Hodgkin’s disease induction failure: a case-control study. Societe Francaise de Greffe de Moelle. J Clin Oncol. 1999;17:222–9.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Reece DE, Barnett MJ, Shepherd JD, et al. High dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV 1/2 P) and autologous transplantation for patients with Hodgkin’s disease who fail to enter a complete remission after combination chemotherapy. Blood. 1995;86:451–6.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Linch DC, Winfield D, Goldstone AH, et al. Dose intensification with autologous bone marrow transplantation in relapsed and resistant Hodgkin’s disease: results of a BNLI randomised trial. Lancet. 1993;341:1051–4.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Schmitz N, Pfistner B, Sextro M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial. Lancet. 2002;359:2065–71.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Kewalramani T, Nimer SD, Zelenetz AD, et al. Progressive disease following autologous transplantation in patients with chemosensitive relapsed or primary refractory Hodgkin’s disease or aggressive non-Hodgkin’s lymphoma. Bone Marrow Transplant. 2003;32:673–9.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Devizzi L, Santoro A, Bonfante V, et al. Vinorelbine: a new promising drug in Hodgkin’s disease. Leuk Lymphoma. 1996;22:409–14.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Santoro A, Bredenfeld H, Devizzi L, et al. Gemcitabinen in the treatment of refractory Hodgkin’s disease: results of a multicenter phase II study. J Clin Oncol. 2000;18:2615–9.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Younes A, Bartlett NL, Leonard JP, et al. Brentuximab vedotin (SGN-35) for relapsed CD30- positive lymphomas. N Engl J Med. 2010;363:1812–21.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30:2183–9.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372:311–9.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Armand P, Shipp MA, Ribrag V, et al. PD-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure: safety, efficacy, and biomarker assessment. In: 57th ASH annual meeting 2015; abstract 584.Google Scholar
  104. 104.
    Herbaux C, Gauthier J, Brice P, et al. Nivolumab is effective and reasonably safe in relapsed or refractory Hodgkin’s lymphoma after allogeneic hematopoietic cell transplantation: a study from the Lysa and SFGM-TC. In: 57th ASH annual meeting 2015; abstract 3979.Google Scholar
  105. 105.
    Zhou N, Moradei O, Raeppel S, et al. Discovery of N-(2-aminophenyl)24-[(4-pyridin-3-ylpyrimidin- 2-ylamino)methyl]benzamide (MGCD0103), an orally active histone deacetylase inhibitor. J Med Chem. 2008;51:4072–5.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Fournel M, Bonfils C, Hou Y, et al. MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo. Mol Cancer Ther. 2008;7:759–68.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Johnston PB, Pinter-Brown L, Rogerio J, et al. Everolimus for relapsed/refractory classical Hodgkin lymphoma: multicenter, open-label, single-arm, phase 2 study. In: 54th ASH annual meeting 2012; abstract 2740.Google Scholar
  108. 108.
    Younes A, Oki Y, Bociek RG, et al. Mocetinostat for relapsed classical Hodgkin’s lymphoma: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2011;12:1222–8.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Meadows SA, Vega F, Kashishian A, et al. PI3Kdelta inhibitor, GS-1101 (CAL-101), attenuates pathway signaling, induces apoptosis, and overcomes signals from the microenvironment in cellular models of Hodgkin lymphoma. Blood. 2012;119:1897–900.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the imaging subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007;25:571–8.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Brig Tathagata Chatterjee
    • 1
  • Ankur Ahuja
    • 2
  1. 1.Department of Lab Sciences and Molecular MedicineAH (R&R)New DelhiIndia
  2. 2.Army Hospital (R&R)New DelhiIndia

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