Advertisement

Treatment and Prognosis

Chapter
  • 623 Downloads
Part of the Molecular Pathology Library book series (MPLB)

Abstract

This chapter will outline the current state of the art of the treatment for Hodgkin lymphoma (HL) with a focus on prognostic factors and risk assessment tools. For newly diagnosed patients with HL, the goal of treatment should be a therapeutic strategy which maximizes the possibility of cure while minimizing the risk of long-term toxicity. Here we discuss clinical prognostic scoring systems, positron emission tomography (PET), and biomarkers, currently used or under investigation, as guide to therapeutic decision making. We further discuss the current standards for first-line therapy of HL, with a special focus on risk-adapted approaches. For relapsed patients we discuss standard treatments and highlight newly approved and promising immunotherapy. Finally we discuss treatment standards for special classes of patients: the elderly, pediatric patients, and patients with lymphocyte predominant (LP) HL. This is an exciting time, as our knowledge of HL biology deepens, evolving risk assessment tools model new treatment strategies, and new therapies are approved, leading the way to patient tailored approaches.

Keywords

Hodgkin lymphoma Risk assessment Tumor-associated macrophages Prognostic markers Biomarkers Therapy Upfront therapy Risk-adapted therapy Relapsed disease Checkpoint inhibitors 

References

  1. Advani RH, Horning SJ, Hoppe RT, Daadi S, Allen J, Natkunam Y et al (2014) Mature results of a phase II study of rituximab therapy for nodular lymphocyte-predominant Hodgkin lymphoma. J Clin Oncol 32(9):912–918CrossRefPubMedGoogle Scholar
  2. Akhtar S, Al-Sugair AS, Abouzied M, Alkadhi Y, Dingle M, Abdelsalam M et al (2013) Pre-transplant FDG-PET-based survival model in relapsed and refractory Hodgkin’s lymphoma: outcome after high-dose chemotherapy and auto-SCT. Bone Marrow Transplant 48(12):1530–1536CrossRefPubMedGoogle Scholar
  3. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M et al (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372(4):311–319CrossRefPubMedGoogle Scholar
  4. Baetz T, Belch A, Couban S, Imrie K, Yau J, Myers R et al (2003) Gemcitabine, dexamethasone and cisplatin is an active and non-toxic chemotherapy regimen in relapsed or refractory Hodgkin’s disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol 14(12):1762–1767CrossRefPubMedGoogle Scholar
  5. Barrington SF, Kirkwood AA, Franceschetto A, Fulham MJ, Roberts TH, Almquist H et al (2016) PET-CT for staging and early response: results from the response-adapted therapy in advanced Hodgkin lymphoma study. Blood 127(12):1531–1538CrossRefPubMedGoogle Scholar
  6. Bartlett NL, Niedzwiecki D, Johnson JL, Friedberg JW, Johnson KB, van Besien K et al (2007) Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin’s lymphoma: CALGB 59804. Ann Oncol 18(6):1071–1079CrossRefPubMedGoogle Scholar
  7. Behringer K, Goergen H, Hitz F, Zijlstra JM, Greil R, Markova J et al (2015) Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin’s lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet 385(9976):1418–1427CrossRefPubMedGoogle Scholar
  8. Boll B, Goergen H, Arndt N, Meissner J, Krause SW, Schnell R et al (2013) Relapsed Hodgkin lymphoma in older patients: a comprehensive analysis from the German Hodgkin study group. J Clin Oncol 31(35):4431–4437CrossRefPubMedGoogle Scholar
  9. Boll B, Goergen H, Behringer K, Brockelmann PJ, Hitz F, Kerkhoff A et al (2016) Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood 127(18):2189–2192CrossRefPubMedGoogle Scholar
  10. Bonadonna G, Zucali R, Monfardini S, De Lena M, Uslenghi C (1975) Combination chemotherapy of Hodgkin’s disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer 36(1):252–259CrossRefPubMedGoogle Scholar
  11. Bonadonna G, Valagussa P, Santoro A (1986) Alternating non-cross-resistant combination chemotherapy or MOPP in stage IV Hodgkin’s disease. A report of 8-year results. Ann Intern Med 104(6):739–746CrossRefPubMedGoogle Scholar
  12. Borchmann P, Haverkamp H, Diehl V, Cerny T, Markova J, Ho AD et al (2011) Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage Hodgkin’s lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. J Clin Oncol 29(32):4234–4242CrossRefPubMedGoogle Scholar
  13. Borchmann PED, Pluetschow A et al (2015) Targeted BEACOPP variants in patients with newly diagnosed advanced stage classical Hodgkin lymphoma: final analysis of a randomized phase II study [ASH abstract 580]. Blood 126(Suppl 23):580Google Scholar
  14. Brandwein JM, Callum J, Sutcliffe SB, Scott JG, Keating A (1990) Evaluation of cytoreductive therapy prior to high dose treatment with autologous bone marrow transplantation in relapsed and refractory Hodgkin’s disease. Bone Marrow Transplant 5(2):99–103PubMedGoogle Scholar
  15. Canellos GP, Mauch P (2010) What is the appropriate systemic chemotherapy for lymphocyte-predominant Hodgkin’s lymphoma? J Clin Oncol 28(1):e8CrossRefPubMedGoogle Scholar
  16. Canellos GP, Rosenberg SA, Friedberg JW, Lister TA, Devita VT (2014) Treatment of Hodgkin lymphoma: a 50-year perspective. J Clin Oncol 32(3):163–168CrossRefPubMedGoogle Scholar
  17. Carde P, Karrasch M, Fortpied C, Brice P, Khaled H, Casasnovas O 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. J Clin Oncol 34(17):2028–2036CrossRefPubMedGoogle Scholar
  18. Chen R, Palmer JM, Martin P, Tsai N, Kim Y, Chen BT et al (2015) 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 21(12):2136–2140CrossRefPubMedPubMedCentralGoogle Scholar
  19. Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ et al (2016a) Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood 128:1562–1566CrossRefPubMedPubMedCentralGoogle Scholar
  20. Chen RZP, Fanale M et al (2016b) Pembrolizumab for relapsed/refractory classical Hodgkin lymphoma (R/R cHL): phase 2 KEYNOTE-087 study. J Clin Oncol 2016(Suppl; abstr 7555):34CrossRefGoogle Scholar
  21. Colwill R, Crump M, Couture F, Danish R, Stewart AK, Sutton DM et al (1995) Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin’s disease before intensive therapy and autologous bone marrow transplantation. J Clin Oncol 13(2):396–402CrossRefPubMedGoogle Scholar
  22. Connors JM, Klimo P, Adams G, Burns BF, Cooper I, Meyer RM et al (1997) Treatment of advanced Hodgkin’s disease with chemotherapy—comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group. J Clin Oncol 15(4):1638–1645CrossRefPubMedGoogle Scholar
  23. Devillier R, Coso D, Castagna L, Brenot Rossi I, Anastasia A, Chiti A et al (2012) Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy. Haematologica 97(7):1073–1079CrossRefPubMedPubMedCentralGoogle Scholar
  24. Diefenbach CS, Li H, Hong F, Gordon LI, Fisher RI, Bartlett NL et al (2015a) Evaluation of the International Prognostic Score (IPS-7) and a Simpler Prognostic Score (IPS-3) for advanced Hodgkin lymphoma in the modern era. Br J Haematol 171(4):530–538CrossRefPubMedPubMedCentralGoogle Scholar
  25. Diefenbach CHF, Cohen J et al (2015b) Preliminary safety and efficacy of the combination of brentuximab vedotin and ipilimumab in relapsed/refractory Hodgkin lymphoma: a trial of the ECOG-ACRIN Cancer Research Group (E4412). Blood 126:585Google Scholar
  26. Diehl V, Sextro M, Franklin J, Hansmann ML, Harris N, Jaffe E et al (1999) Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin’s disease and lymphocyte-rich classical Hodgkin’s disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin’s Disease. J Clin Oncol 17(3):776–783CrossRefPubMedGoogle Scholar
  27. Duggan DB, Petroni GR, Johnson JL, Glick JH, Fisher RI, Connors JM et al (2003) Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin’s disease: report of an intergroup trial. J Clin Oncol 21(4):607–614CrossRefPubMedGoogle Scholar
  28. Eich HT, Diehl V, Gorgen H, Pabst T, Markova J, Debus J et al (2010) 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 28(27):4199–4206CrossRefPubMedGoogle Scholar
  29. Eichenauer DA, Fuchs M, Pluetschow A, Klimm B, Halbsguth T, Boll B et al (2011) Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood 118(16):4363–4365CrossRefPubMedGoogle Scholar
  30. Engert A, Diehl V, Franklin J, Lohri A, Dorken B, Ludwig WD et al (2009) Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin’s lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol 27(27):4548–4554CrossRefPubMedGoogle Scholar
  31. Engert A, Plutschow A, Eich HT, Lohri A, Dorken B, Borchmann P et al (2010) Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N Engl J Med 363(7):640–652CrossRefPubMedGoogle Scholar
  32. Engert A, Haverkamp H, Kobe C, Markova J, Renner C, Ho A et al (2012) Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet 379(9828):1791–1799CrossRefPubMedGoogle Scholar
  33. Evens AM, Helenowski I, Ramsdale E, Nabhan C, Karmali R, Hanson B et al (2012) A retrospective multicenter analysis of elderly Hodgkin lymphoma: outcomes and prognostic factors in the modern era. Blood 119(3):692–695CrossRefPubMedGoogle Scholar
  34. Fanale M, Lai CM et al (2010) Outcomes of nodular lymphocyte predominant Hodgkin’s lymphoma (NLPHL) patients treated with R-CHOP. Blood 116:2812CrossRefGoogle Scholar
  35. Fanale MA, Forero-Torres A, Rosenblatt JD, Advani RH, Franklin AR, Kennedy DA et al (2012) A phase I weekly dosing study of brentuximab vedotin in patients with relapsed/refractory CD30-positive hematologic malignancies. Clin Cancer Res 18(1):248–255CrossRefPubMedGoogle Scholar
  36. Federico M, Luminari S, Iannitto E, Polimeno G, Marcheselli L, Montanini A et al (2009) ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin’s lymphoma: results from the HD2000 Gruppo Italiano per lo Studio dei Linfomi trial. J Clin Oncol 27(5):805–811CrossRefPubMedGoogle Scholar
  37. Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ et al (2014) 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 32(32):3651–3658CrossRefPubMedPubMedCentralGoogle Scholar
  38. Gallamini A, Hutchings M, Rigacci L, Specht L, Merli F, Hansen M et al (2007) 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 25(24):3746–3752CrossRefPubMedGoogle Scholar
  39. Gandhi MK, Lambley E, Burrows J, Dua U, Elliott S, Shaw PJ et al (2006) Plasma Epstein-Barr virus (EBV) DNA is a biomarker for EBV-positive Hodgkin’s lymphoma. Clin Cancer Res 12(2):460–464CrossRefPubMedGoogle Scholar
  40. Gentzler RD, Evens AM, Rademaker AW, Weitner BB, Mittal BB, Dillehay GL et al (2014) F-18 FDG-PET predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem-cell transplantation for relapsed and refractory Hodgkin lymphoma. Br J Haematol 165(6):793–800CrossRefPubMedGoogle Scholar
  41. Gopal AK, Bartlett NL, Forero-Torres A, Younes A, Chen R, Friedberg JW et al (2014) Brentuximab vedotin in patients aged 60 years or older with relapsed or refractory CD30-positive lymphomas: a retrospective evaluation of safety and efficacy. Leuk Lymphoma 55(10):2328–2334CrossRefPubMedGoogle Scholar
  42. Gordon LI, Hong F, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD 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). J Clin Oncol 31(6):684–691CrossRefPubMedGoogle Scholar
  43. Halbsguth TV, Boll B, Borchmann P, Diehl V (2011) The unique characteristics and management of patients over 60 years of age with classic Hodgkin lymphoma. Curr Hematol Malig Rep 6(3):164–171CrossRefPubMedGoogle Scholar
  44. Hasenclever D, Diehl V (1998) A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s Disease. N Engl J Med 339(21):1506–1514CrossRefPubMedGoogle Scholar
  45. Hawkes EA, Barton S, Cunningham D, Peckitt C, Chua S, Wotherspoon A et al (2014) GEM-P chemotherapy is active in the treatment of relapsed Hodgkin lymphoma. Ann Hematol 93(5):827–834CrossRefPubMedGoogle Scholar
  46. Hay AE, Klimm B, Chen BE, Goergen H, Shepherd LE, Fuchs M et al (2013) An individual patient-data comparison of combined modality therapy and ABVD alone for patients with limited-stage Hodgkin lymphoma. Ann Oncol 24(12):3065–3069CrossRefPubMedGoogle Scholar
  47. Hodgson DC, Hudson MM, Constine LS (2007) Pediatric Hodgkin lymphoma: maximizing efficacy and minimizing toxicity. Semin Radiat Oncol 17(3):230–242CrossRefPubMedGoogle Scholar
  48. Howlander N NA, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL (1975–2013) SEER cancer statistics review. SEERcancergovGoogle Scholar
  49. Hutchings M, Loft A, Hansen M, Pedersen LM, Buhl T, Jurlander J et al (2006) FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood 107(1):52–59CrossRefPubMedGoogle Scholar
  50. Jagadeesh D, Diefenbach C, Evens AM (2013) XII. Hodgkin lymphoma in older patients: challenges and opportunities to improve outcomes. Hematol Oncol 31(Suppl 1):69–75CrossRefPubMedGoogle Scholar
  51. Johnson P, Federico M, Kirkwood A, Fossa A, Berkahn L, Carella A et al (2016) Adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. N Engl J Med 374(25):2419–2429CrossRefPubMedPubMedCentralGoogle Scholar
  52. Josting A, Rudolph C, Mapara M, Glossmann JP, Sieniawski M, Sieber M et al (2005) Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma: results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG). Ann Oncol 16(1):116–123CrossRefPubMedGoogle Scholar
  53. Kamper P, Bendix K, Hamilton-Dutoit S, Honore B, Nyengaard JR, d’Amore F (2011) Tumor-infiltrating macrophages correlate with adverse prognosis and Epstein-Barr virus status in classical Hodgkin’s lymphoma. Haematologica 96(2):269–276CrossRefPubMedGoogle Scholar
  54. Kanakry JA, Li H, Gellert LL, Lemas MV, Hsieh WS, Hong F et al (2013) Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma: correlative analysis from a large North American cooperative group trial. Blood 121(18):3547–3553CrossRefPubMedPubMedCentralGoogle Scholar
  55. Kapatai G, Murray P (2007) Contribution of the Epstein Barr virus to the molecular pathogenesis of Hodgkin lymphoma. J Clin Pathol 60(12):1342–1349CrossRefPubMedPubMedCentralGoogle Scholar
  56. Karuturi M, Hosing C, Fanale M, Medeiros LJ, Alousi AM, de Lima MJ et al (2013) High-dose chemotherapy and autologous stem cell transplantation for nodular lymphocyte-predominant Hodgkin lymphoma. Biol Blood Marrow Transplant 19(6):991–994CrossRefPubMedPubMedCentralGoogle Scholar
  57. Keller H, Goda JS, Vines DC, Lockwood G, Tsang R (2010) Quantification of local tumor response to fractionated radiation therapy for non-Hodgkin lymphoma using weekly 18F-FDG PET/CT imaging. Int J Radiat Oncol Biol Phys 76(3):850–858CrossRefPubMedGoogle Scholar
  58. Kewalramani T, Nimer SD, Zelenetz AD, Malhotra S, Qin J, Yahalom J et al (2003) 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 32(7):673–679CrossRefPubMedGoogle Scholar
  59. Linch DC, Winfield D, Goldstone AH, Moir D, Hancock B, McMillan A et al (1993) Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin’s disease: results of a BNLI randomised trial. Lancet 341(8852):1051–1054CrossRefPubMedGoogle Scholar
  60. Marri PR, Hodge LS, Maurer MJ, Ziesmer SC, Slager SL, Habermann TM et al (2013) Prognostic significance of pretreatment serum cytokines in classical Hodgkin lymphoma. Clin Cancer Res 19(24):6812–6819CrossRefPubMedGoogle Scholar
  61. Mauz-Korholz C, Hasenclever D, Dorffel W, Ruschke K, Pelz T, Voigt A et al (2010) 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 28(23):3680–3686CrossRefPubMedGoogle Scholar
  62. Merli F, Luminari S, Gobbi PG, Cascavilla N, Mammi C, Ilariucci F 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. J Clin Oncol 34(11):1175–1181CrossRefPubMedGoogle Scholar
  63. Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Bezjak A, Wells WA et al (2005) Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin’s lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. J Clin Oncol 23(21):4634–4642CrossRefPubMedGoogle Scholar
  64. Moccia AA, Donaldson J, Chhanabhai M, Hoskins PJ, Klasa RJ, Savage KJ et al (2012) International Prognostic Score in advanced-stage Hodgkin’s lymphoma: altered utility in the modern era. J Clin Oncol 30(27):3383–3388CrossRefPubMedGoogle Scholar
  65. Moskowitz CH, Nimer SD, Zelenetz AD, Trippett T, Hedrick EE, Filippa DA et al (2001) A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood 97(3):616–623CrossRefPubMedGoogle Scholar
  66. Moskowitz AJ, Yahalom J, Kewalramani T, Maragulia JC, Vanak JM, Zelenetz AD et al (2010) Pretransplantation functional imaging predicts outcome following autologous stem cell transplantation for relapsed and refractory Hodgkin lymphoma. Blood 116(23):4934–4937CrossRefPubMedPubMedCentralGoogle Scholar
  67. Moskowitz AJ, Hamlin PA Jr, Perales MA, Gerecitano J, Horwitz SM, Matasar MJ et al (2013) Phase II study of bendamustine in relapsed and refractory Hodgkin lymphoma. J Clin Oncol 31(4):456–460CrossRefPubMedGoogle Scholar
  68. Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH et al (2015a) Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 385(9980):1853–1862CrossRefPubMedGoogle Scholar
  69. Moskowitz AJ, Schoder H, Yahalom J, McCall SJ, Fox SY, Gerecitano J et al (2015b) PET-adapted sequential salvage therapy with brentuximab vedotin followed by augmented ifosamide, carboplatin, and etoposide for patients with relapsed and refractory Hodgkin’s lymphoma: a non-randomised, open-label, single-centre, phase 2 study. Lancet Oncol 16(3):284–292CrossRefPubMedGoogle Scholar
  70. Mounier N, Brice P, Bologna S, Briere J, Gaillard I, Heczko M et al (2014) ABVD (8 cycles) versus BEACOPP (4 escalated cycles >/= 4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol 25(8):1622–1628CrossRefPubMedGoogle Scholar
  71. Nogova L, Reineke T, Eich HT, Josting A, Muller-Hermelink HK, Wingbermuhle K et al (2005) Extended field radiotherapy, combined modality treatment or involved field radiotherapy for patients with stage IA lymphocyte-predominant Hodgkin’s lymphoma: a retrospective analysis from the German Hodgkin Study Group (GHSG). Ann Oncol 16(10):1683–1687CrossRefPubMedGoogle Scholar
  72. Nogova L, Reineke T, Brillant C, Sieniawski M, Rudiger T, Josting A et al (2008) Lymphocyte-predominant and classical Hodgkin’s lymphoma: a comprehensive analysis from the German Hodgkin Study Group. J Clin Oncol 26(3):434–439CrossRefPubMedGoogle Scholar
  73. Press OW, Li H, Schoder H, Straus DJ, Moskowitz CH, LeBlanc M et al (2016) US Intergroup trial of response-adapted therapy for stage III to IV Hodgkin lymphoma using early interim fluorodeoxyglucose-positron emission tomography imaging: Southwest Oncology Group S0816. J Clin Oncol 34(17):2020–2027CrossRefPubMedPubMedCentralGoogle Scholar
  74. Radford J, Illidge T, Counsell N, Hancock B, Pettengell R, Johnson P et al (2015) Results of a trial of PET-directed therapy for early-stage Hodgkin’s lymphoma. N Engl J Med 372(17):1598–1607CrossRefPubMedGoogle Scholar
  75. Raemaekers JM (2015) Early FDG-PET adapted treatment improves the outcome of early FDG-PET-positive patients with stages I/II Hodgkin lymphoma (HL): final results of the randomized intergroup EORTC/LYSA/FIL H10 trial. 13th International Conference on Malignant Lymphoma (ICML) in LuganoGoogle Scholar
  76. Raemaekers JM, Andre MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E et al (2014) Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol 32(12):1188–1194CrossRefPubMedGoogle Scholar
  77. Reichel J, Chadburn A, Rubinstein PG, Giulino-Roth L, Tam W, Liu Y et al (2015) Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells. Blood 125(7):1061–1072CrossRefPubMedGoogle Scholar
  78. Robinson SP, Goldstone AH, Mackinnon S, Carella A, Russell N, de Elvira CR et al (2002) Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Blood 100(13):4310–4316CrossRefPubMedGoogle Scholar
  79. Roemer MG, Advani RH, Ligon AH, Natkunam Y, Redd RA, Homer H et al (2016) PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. J Clin Oncol 34:2690–2697CrossRefPubMedPubMedCentralGoogle Scholar
  80. Santoro A, Bredenfeld H, Devizzi L, Tesch H, Bonfante V, Viviani S et al (2000) Gemcitabine in the treatment of refractory Hodgkin’s disease: results of a multicenter phase II study. J Clin Oncol 18(13):2615–2619CrossRefPubMedGoogle Scholar
  81. Sauer M, Plutschow A, Jachimowicz RD, Kleefisch D, Reiners KS, Ponader S et al (2013) Baseline serum TARC levels predict therapy outcome in patients with Hodgkin lymphoma. Am J Hematol 88(2):113–115CrossRefPubMedGoogle Scholar
  82. Savage KJ, Skinnider B, Al-Mansour M, Sehn LH, Gascoyne RD, Connors JM (2011) Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome. Blood 118(17):4585–4590CrossRefPubMedGoogle Scholar
  83. Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M et al (2002) Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial. Lancet 359(9323):2065–2071CrossRefPubMedGoogle Scholar
  84. Schulz H, Rehwald U, Morschhauser F, Elter T, Driessen C, Rudiger T et al (2008) Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood 111(1):109–111CrossRefPubMedGoogle Scholar
  85. Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R et al (2009) 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 114(10):2051–2059CrossRefPubMedPubMedCentralGoogle Scholar
  86. Scott DW, Chan FC, Hong F, Rogic S, Tan KL, Meissner B et al (2013) Gene expression-based model using formalin-fixed paraffin-embedded biopsies predicts overall survival in advanced-stage classical Hodgkin lymphoma. J Clin Oncol 31(6):692–700CrossRefPubMedGoogle Scholar
  87. Steidl C, Diepstra A, Lee T, Chan FC, Farinha P, Tan K et al (2012) Gene expression profiling of microdissected Hodgkin Reed-Sternberg cells correlates with treatment outcome in classical Hodgkin lymphoma. Blood 120(17):3530–3540CrossRefPubMedGoogle Scholar
  88. Sureda A, Canals C, Arranz R, Caballero D, Ribera JM, Brune M et al (2012) Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin’s lymphoma. Results of the HDR-ALLO study—a prospective clinical trial by the Grupo Espanol de Linfomas/Trasplante de Medula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Haematologica 97(2):310–317CrossRefPubMedPubMedCentralGoogle Scholar
  89. Tan KL, Scott DW, Hong F, Kahl BS, Fisher RI, Bartlett NL et al (2012) Tumor-associated macrophages predict inferior outcomes in classic Hodgkin lymphoma: a correlative study from the E2496 Intergroup trial. Blood 120(16):3280–3287CrossRefPubMedPubMedCentralGoogle Scholar
  90. Tebbi CK, Mendenhall NP, London WB, Williams JL, Hutchison RE, Fitzgerald TJ et al (2012) Response-dependent and reduced treatment in lower risk Hodgkin lymphoma in children and adolescents, results of P9426: a report from the Children’s Oncology Group. Pediatr Blood Cancer 59(7):1259–1265CrossRefPubMedPubMedCentralGoogle Scholar
  91. Viviani S, Bonadonna G, Santoro A, Bonfante V, Zanini M, Devizzi L et al (1996) Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin’s disease: ten-year results. J Clin Oncol 14(5):1421–1430CrossRefPubMedGoogle Scholar
  92. Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V et al (2011) ABVD versus BEACOPP for Hodgkin’s lymphoma when high-dose salvage is planned. N Engl J Med 365(3):203–212CrossRefPubMedGoogle Scholar
  93. von Tresckow B, Plutschow A, Fuchs M, Klimm B, Markova J, Lohri A et al (2012) Dose-intensification in early unfavorable Hodgkin’s lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol 30(9):907–913CrossRefGoogle Scholar
  94. Weihrauch MR, Manzke O, Beyer M, Haverkamp H, Diehl V, Bohlen H et al (2005) Elevated serum levels of CC thymus and activation-related chemokine (TARC) in primary Hodgkin’s disease: potential for a prognostic factor. Cancer Res 65(13):5516–5519CrossRefPubMedGoogle Scholar
  95. Wilder RB, Schlembach PJ, Jones D, Chronowski GM, Ha CS, Younes A et al (2002) European Organization for Research and Treatment of Cancer and Groupe d’Etude des Lymphomes de l’Adulte very favorable and favorable, lymphocyte-predominant Hodgkin disease. Cancer 94(6):1731–1738CrossRefPubMedGoogle Scholar
  96. Wirth A, Yuen K, Barton M, Roos D, Gogna K, Pratt G et al (2005) Long-term outcome after radiotherapy alone for lymphocyte-predominant Hodgkin lymphoma: a retrospective multicenter study of the Australasian Radiation Oncology Lymphoma Group. Cancer 104(6):1221–1229CrossRefPubMedGoogle Scholar
  97. Xing KH, Connors JM, Lai A, Al-Mansour M, Sehn LH, Villa D et al (2014) Advanced-stage nodular lymphocyte predominant Hodgkin lymphoma compared with classical Hodgkin lymphoma: a matched pair outcome analysis. Blood 123(23):3567–3573CrossRefPubMedGoogle Scholar
  98. Younes A, Bartlett NL, Leonard JP, Kennedy DA, Lynch CM, Sievers EL et al (2010) Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med 363(19):1812–1821CrossRefPubMedGoogle Scholar
  99. Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ et al (2012) Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol 30(18):2183–2189CrossRefPubMedPubMedCentralGoogle Scholar
  100. Younes A, Connors JM, Park SI, Fanale M, O’Meara MM, Hunder NN et al (2013) Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin’s lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol 14(13):1348–1356CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Center for Lymphoid Malignancies, Herbert Irving Comprehensive Cancer CenterColumbia University Medical CenterNew YorkUSA
  2. 2.NYU Perlmutter Cancer Center, NYU Cancer CenterNew YorkUSA

Personalised recommendations