Vol 8, No 3 (2017)
Review paper
Published online: 2017-11-23

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Diagnosis and treatment of patients with Hodgkin lymphoma

Tomasz Wróbel1, Bartosz Puła2
Hematologia 2017;8(3):163-176.

Abstract

Hodgkin lymphoma (HL) is a rare B-cell derived lymphoid malignancy. Its typical feature is the presence of small number of tumor cells surrounded by immune cell infiltrate of immunosuppressive character. Two entities of HL are distinguished: classical HL and nodular lymphocyte predominant HL. Assessment of clinical advancement stage and prognostic factors is important for tailoring appropriate therapy based on chemotherapy and radiotherapy. Prognosis in HL is good with cure rate reaching almost 80%. About 10% of patients (especially in advanced stages) does not achieve complete remission. In 20–30% patients, who initially achieved a response, relapses occur. For these patients’, besides chemotherapy, treatment with brentuximab vedotin, PD-1 inhibitors, autologous or allogeneic hematopoietic stem cell transplantation, or participation in clinical trial comprise poten¬tial therapy options. In this publication, we discuss the guidelines of diagnosis and treatment of HL.

References

  1. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016; 127(20): 2375–2390.
  2. Swerdlow, S.H., et al., WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Fourth Edition.IARC. 2008.
  3. Glaser SL, Jarrett RF. The epidemiology of Hodgkin's disease. Baillieres Clin Haematol. 1996; 9(3): 401–416.
  4. Juszczyński P. Mikrośrodowisko komórek Reed-Sternberga w klasycznym chłoniaku Hodgkina — rola patogenetyczna i cel terapeutyczny. Hematologia, 2011. Hematologia. 2011; 2(1): 1–14.
  5. Diehl V, Burrichter H, Schaadt M, et al. Hodgkin's disease cell lines: characteristics and biological activities. Haematol Blood Transfus. 1983; 28: 411–417.
  6. Irsch J, Nitsch S, Hansmann ML, et al. Isolation of viable Hodgkin and Reed-Sternberg cells from Hodgkin disease tissues. Proc Natl Acad Sci U S A. 1998; 95(17): 10117–10122.
  7. Döring C, Hansmann ML, Agostinelli C, et al. A novel immunohistochemical classifier to distinguish Hodgkin lymphoma from ALK anaplastic large cell lymphoma. Mod Pathol. 2014; 27(10): 1345–1354.
  8. Pinkus GS, Said JW. Hodgkin's disease, lymphocyte predominance type, nodular--further evidence for a B cell derivation. L & H variants of Reed-Sternberg cells express L26, a pan B cell marker. Am J Pathol. 1988; 133(2): 211–217.
  9. Ansell SM. Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016; 91(4): 434–442.
  10. Savage KJ, Mottok A, Fanale M. Nodular lymphocyte-predominant Hodgkin lymphoma. Semin Hematol. 2016; 53(3): 190–202.
  11. Kanzler H, Küppers R, Hansmann ML, et al. 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(4): 1495–1505.
  12. Kuppers R, Rajewsky K, Zhao M, et al. Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development. Proc Natl Acad Sci U S A. 1994; 91(23): 10962–10966.
  13. Küppers R, Rajewsky K, Zhao M, et al. Hodgkin's disease: clonal Ig gene rearrangements in Hodgkin and Reed-Sternberg cells picked from histological sections. Ann N Y Acad Sci. 1995; 764: 523–524.
  14. Re D, Müschen M, Ahmadi T, et al. Oct-2 and Bob-1 deficiency in Hodgkin and Reed Sternberg cells. Cancer Res. 2001; 61(5): 2080–2084.
  15. 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(2): 496–501.
  16. Schwarzer R, Jundt F. Notch and NF-κB signaling pathways in the biology of classical Hodgkin lymphoma. Curr Mol Med. 2011; 11(3): 236–245.
  17. Schwarzer R, Dörken B, Jundt F. Notch is an essential upstream regulator of NF-κB and is relevant for survival of Hodgkin and Reed-Sternberg cells. Leukemia. 2012; 26(4): 806–813.
  18. Grufferman S, Cole P, Smith PG, et al. Hodgkin's disease in siblings. N Engl J Med. 1977; 296(5): 248–250.
  19. Mack TM, Cozen W, Shibata DK, et al. Concordance for Hodgkin's disease in identical twins suggesting genetic susceptibility to the young-adult form of the disease. N Engl J Med. 1995; 332(7): 413–418.
  20. Horwitz M, Wiernik PH. Pseudoautosomal linkage of Hodgkin disease. Am J Hum Genet. 1999; 65(5): 1413–1422.
  21. Azhar M, Din HUd, Muhammad I, et al. Frequency of epstein-barr virus in classical hodgkin Lymphoma. J Ayub Med Coll Abbottabad. 2016; 28(2): 271–275.
  22. Weiss LM, Strickler JG, Warnke RA, et al. Epstein-Barr viral DNA in tissues of Hodgkin's disease. Am J Pathol. 1987; 129(1): 86–91.
  23. Franceschi S, Dal Maso L, La Vecchia C. Advances in the epidemiology of HIV-associated non-Hodgkin's lymphoma and other lymphoid neoplasms. Int J Cancer. 1999; 83(4): 481–485, doi: 10.1002/(sici)1097-0215(19991112)83:4<481::aid-ijc8>3.3.co;2-x.
  24. Andrieu JM, Roithmann S, Tourani JM, et al. Hodgkin's disease during HIV1 infection: the French registry experience. French Registry of HIV-associated Tumors. Ann Oncol. 1993; 4(8): 635–641.
  25. Tirelli U, Errante D, Dolcetti R, et al. Hodgkin's disease and human immunodeficiency virus infection: clinicopathologic and virologic features of 114 patients from the Italian Cooperative Group on AIDS and Tumors. J Clin Oncol. 1995; 13(7): 1758–1767.
  26. Diehl V, Sextro M, Franklin J, et al. 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. 1999; 17(3): 776–783.
  27. Barrington SF, Mikhaeel NG, Kostakoglu L, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014; 32(27): 3048–3058.
  28. Cheson BD, Fisher RI, Barrington SF, et al. Alliance, Australasian Leukaemia and Lymphoma Group, Eastern Cooperative Oncology Group, European Mantle Cell Lymphoma Consortium, Italian Lymphoma Foundation, European Organisation for Research, Treatment of Cancer/Dutch Hemato-Oncology Group, Grupo Español de Médula Ósea, German High-Grade Lymphoma Study Group, German Hodgkin's Study Group, Japanese Lymphorra Study Group, Lymphoma Study Association, NCIC Clinical Trials Group, Nordic Lymphoma Study Group, Southwest Oncology Group, United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014; 32(27): 3059–3068.
  29. Carbone PP, Kaplan HS, Musshoff K, et al. Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res. 1971; 31(11): 1860–1861.
  30. 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(11): 1630–1636.
  31. Jerusalem G, Beguin Y, Fassotte MF, et al. Whole-body positron emission tomography using 18F-fluorodeoxyglucose compared to standard procedures for staging patients with Hodgkin's disease. Haematologica. 2001; 86(3): 266–273.
  32. 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(24): 3746–3752.
  33. Tubiana M. Toward comprehensive management tailored to prognostic factors of patients with clinical stages I and II in Hodgkin's disease. The EORTC Lymphoma Group controlled clinical trials: 1964-1987. Blood. 1989; 73(1): 47–56.
  34. Diehl V, Stein H, Hummel M, et al. Hodgkin's lymphoma: biology and treatment strategies for primary, refractory, and relapsed disease. Hematology Am Soc Hematol Educ Program. 2003: 225–247.
  35. Hasenclever D, Diehl V, Armitage J, et al. A Prognostic Score for Advanced Hodgkin's Disease. N Engl J Med. 1998; 339(21): 1506–1514.
  36. Hutchings M, Loft A, Hansen M, et al. FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood. 2006; 107(1): 52–59.
  37. Mikhaeel NG, Hutchings M, Fields PA, et al. FDG-PET after two to three cycles of chemotherapy predicts progression-free and overall survival in high-grade non-Hodgkin lymphoma. Ann Oncol. 2005; 16(9): 1514–1523.
  38. Coyle M, Kostakoglu L, Evens AM. The evolving role of response-adapted PET imaging in Hodgkin lymphoma. Ther Adv Hematol. 2016; 7(2): 108–125.
  39. Radford J, Illidge T, Counsell N, et al. Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. N Engl J Med. 2015; 372(17): 1598–1607.
  40. André MPE, Girinsky T, Federico M, et al. Early Positron Emission Tomography Response-Adapted Treatment in Stage I and II Hodgkin Lymphoma: Final Results of the Randomized EORTC/LYSA/FIL H10 Trial. J Clin Oncol. 2017; 35(16): 1786–1794.
  41. Engert A, Franklin J, Eich HT, et al. Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial. J Clin Oncol. 2007; 25(23): 3495–3502.
  42. Engert A, Plütschow A, Eich HT, et al. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med. 2010; 363(7): 640–652.
  43. Eich H, Diehl V, Görgen H, et al. 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. 2010; 28(27): 4199–4206.
  44. von Tresckow B, Plütschow A, Fuchs M, et al. Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol. 2012; 30(9): 907–913.
  45. van Leeuwen FE, Ng AK. Late sequelae in Hodgkin lymphoma survivors. Hematol Oncol. 2017; 35 Suppl 1: 60–66.
  46. Canellos GP, Anderson JR, Propert KJ, et al. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992; 327(21): 1478–1484.
  47. Viviani S, Bonadonna G, Santoro A, et al. Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin's disease: ten-year results. J Clin Oncol. 1996; 14(5): 1421–1430.
  48. Duggan DB, Petroni GR, Johnson JL, et al. Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial. J Clin Oncol. 2003; 21(4): 607–614.
  49. Engert A, Haverkamp H, Kobe C, et al. German Hodgkin Study Group, Swiss Group for Clinical Cancer Research, Arbeitsgemeinschaft Medikamentöse Tumortherapie. 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. 2012; 379(9828): 1791–1799.
  50. Diehl V, Sieber M, Rüffer U, et al. BEACOPP: an intensified chemotherapy regimen in advanced Hodgkin's disease. The German Hodgkin's Lymphoma Study Group. Ann Oncol. 1997; 8(2): 143–148.
  51. Skoetz N, Trelle S, Rancea M, et al. Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin's lymphoma: a systematic review and network meta-analysis. Lancet Oncol. 2013; 14(10): 943–952.
  52. Viviani S, Zinzani PL, Rambaldi A, et al. Michelangelo Foundation, Gruppo Italiano di Terapie Innovative nei Linfomi, Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011; 365(3): 203–212.
  53. Eichenauer DA, Thielen I, Haverkamp H, et al. Therapy-related acute myeloid leukemia and myelodysplastic syndromes in patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood. 2014; 123(11): 1658–1664.
  54. Engert A, Diehl V, Franklin J, et al. 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. 2009; 27(27): 4548–4554.
  55. Behringer K, Breuer K, Reineke T, et al. German Hodgkin's Lymphoma Study Group. Secondary amenorrhea after Hodgkin's lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: a report from the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 2005; 23(30): 7555–7564.
  56. Van der Kaaij MA, et al. Gonadal Function in Males After Chemotherapy for Early-Stage Hodgkin's Lymphoma Treated in Four Subsequent Trials by the European Organisation for Research and Treatment of Cancer: EORTC Lymphoma Group and the Groupe d'Étude des Lymphomes de l'Adulte. J Clin Oncol. 2007; 25(19): 2825–2832.
  57. Nogová L, Reineke T, Eich HT, et al. 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. 2005; 16(10): 1683–1687.
  58. Nogová L, Reineke T, Brillant C, et al. German Hodgkin Study Group. Lymphocyte-predominant and classical Hodgkin's lymphoma: a comprehensive analysis from the German Hodgkin Study Group. J Clin Oncol. 2008; 26(3): 434–439.
  59. Advani RH, Horning SJ, Hoppe RT, et al. Mature results of a phase II study of rituximab therapy for nodular lymphocyte-predominant Hodgkin lymphoma. J Clin Oncol. 2014; 32(9): 912–918.
  60. Cencini E, Fabbri A, Bocchia M. Rituximab plus ABVD in newly diagnosed nodular lymphocyte-predominant Hodgkin lymphoma. Br J Haematol. 2017; 176(5): 831–833.
  61. Smardova L, Engert A, Haverkamp H, et al. Successful mobilization of peripheral blood stem cells with the DHAP regimen (dexamethasone, cytarabine, cisplatinum) plus granulocyte colony-stimulating factor in patients with relapsed Hodgkin's disease. Leuk Lymphoma. 2005; 46(7): 1017–1022.
  62. Mehrzad V, Ashrafi F, Farrashi AR, et al. Comparison of Ifosfamide, Carboplatin and Etoposide versus Etoposide, Steroid, and Cytarabine Cisplatin as Salvage Chemotherapy in Patients with Refractory or Relapsed Hodgkin's lymphoma. Adv Biomed Res. 2017; 6: 30.
  63. Labrador J, Cabrero-Calvo M, Pérez-López E, et al. ESHAP as salvage therapy for relapsed or refractory Hodgkin's lymphoma. Ann Hematol. 2014; 93(10): 1745–1753.
  64. Rodriguez J, Rodriguez MA, Fayad L, et al. ASHAP: a regimen for cytoreduction of refractory or recurrent Hodgkin's disease. Blood. 1999; 93(11): 3632–3636.
  65. Magagnoli M, Spina M, Balzarotti M, et al. IGEV regimen and a fixed dose of lenograstim: an effective mobilization regimen in pretreated Hodgkin's lymphoma patients. Bone Marrow Transplant. 2007; 40(11): 1019–1025.
  66. Bartlett NL, Niedzwiecki D, Johnson JL, et al. Cancer Leukemia Group B. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin's lymphoma: CALGB 59804. Ann Oncol. 2007; 18(6): 1071–1079.
  67. Baetz T, Belch A, Couban S, et al. 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. 2003; 14(12): 1762–1767.
  68. Josting A, Kàtay I, Rueffer U, et al. Favorable outcome of patients with relapsed or refractory Hodgkin's disease treated with high-dose chemotherapy and stem cell rescue at the time of maximal response to conventional salvage therapy (Dex-BEAM). Ann Oncol. 1998; 9(3): 289–295.
  69. Moreau P, Fleury J, Brice P, et al. Early intensive therapy with autologous stem cell transplantation in advanced Hodgkin's disease: retrospective analysis of 158 cases from the French registry. Bone Marrow Transplant. 1998; 21(8): 787–793.
  70. Brice P, Bouabdallah R, Moreau P, et al. Prognostic factors for survival after high-dose therapy and autologous stem cell transplantation for patients with relapsing Hodgkin's disease: analysis of 280 patients from the French registry. Société Française de Greffe de Moëlle. Bone Marrow Transplant. 1997; 20(1): 21–26.
  71. 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(9323): 2065–2071.
  72. Kusnierz-Glaz CR, Schlegel PG, Wong RM, et al. Influence of age on the outcome of 500 autologous bone marrow transplant procedures for hematologic malignancies. J Clin Oncol. 1997; 15(1): 18–25.
  73. Brice P, Divine M, Simon D, et al. Feasibility of tandem autologous stem-cell transplantation (ASCT) in induction failure or very unfavorable (UF) relapse from Hodgkin's disease (HD). SFGM/GELA Study Group. Ann Oncol. 1999; 10(12): 1485–1488.
  74. Sureda A, Robinson S, Canals C, et al. Reduced-intensity conditioning compared with conventional allogeneic stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2008; 26(3): 455–462.
  75. Robinson SP, Sureda A, Canals C, et al. Lymphoma Working Party of the EBMT. Reduced intensity conditioning allogeneic stem cell transplantation for Hodgkin's lymphoma: identification of prognostic factors predicting outcome. Haematologica. 2009; 94(2): 230–238.
  76. Schmitz N, Sureda A, Robinson S. Allogeneic transplantation of hematopoietic stem cells after nonmyeloablative conditioning for Hodgkin’s disease: indications and results. Semin Oncol. 2004; 31(1): 27–32.
  77. Gonzalez VJ. Role of Radiation Therapy in the Treatment of Hodgkin Lymphoma. Curr Hematol Malig Rep. 2017; 12(3): 244–250.
  78. Devizzi L, Santoro A, Bonfante V, et al. Vinorelbine: a new promising drug in Hodgkin's disease. Leuk Lymphoma. 1996; 22(5-6): 409–414.
  79. Santoro A, Bredenfeld H, Devizzi L, et al. Gemcitabine in the treatment of refractory Hodgkin's disease: results of a multicenter phase II study. J Clin Oncol. 2000; 18(13): 2615–2619.
  80. Younes A, Bartlett NL, Leonard JP, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010; 363(19): 1812–1821.
  81. 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(18): 2183–2189.
  82. Gopal AK, Chen R, Smith SE, et al. Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood. 2015; 125(8): 1236–1243.
  83. Moskowitz CH, Nademanee A, Masszi T, et al. AETHERA Study Group. 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. 2015; 385(9980): 1853–1862.
  84. Younes A, Connors JM, Park SI, et al. 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. 2013; 14(13): 1348–1356.
  85. Carson K, Newsome S, Kim E, et al. Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: A report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project. Cancer. 2014; 120(16): 2464–2471.
  86. von Geldern G, Pardo CA, Calabresi PA, et al. PML-IRIS in a patient treated with brentuximab. Neurology. 2012; 79(20): 2075–2077.
  87. Gandhi MD, Evens AM, Fenske TS, et al. Pancreatitis in patients treated with brentuximab vedotin: a previously unrecognized serious adverse event. Blood. 2014; 123(18): 2895–2897.
  88. Yamamoto R, Nishikori M, Kitawaki T, et al. PD-1-PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma. Blood. 2008; 111(6): 3220–3224.
  89. Armand P, Shipp MA, Ribrag V, et al. Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. J Clin Oncol. 2016 [Epub ahead of print].
  90. Younes A, Santoro A, Shipp M, et al. 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 Oncol. 2016; 17(9): 1283–1294.
  91. Villasboas JC, Ansell SM. Recent advances in the management of Hodgkin lymphoma. F1000Res. 2016; 5.
  92. Bond DA, Alinari L. Emerging treatment options for the management of Hodgkin's lymphoma: clinical utility of nivolumab. J Blood Med. 2017; 8: 41–54.
  93. Maly J, Alinari L. Pembrolizumab in classical Hodgkin's lymphoma. Eur J Haematol. 2016; 97(3): 219–227.
  94. Ng AK, van Leeuwen FE. Hodgkin lymphoma: Late effects of treatment and guidelines for surveillance. Semin Hematol. 2016; 53(3): 209–215.
  95. Moshe Y, Bentur OS, Lishner M, et al. The management of hodgkin lymphomas in pregnancies. Eur J Haematol. 2017 [Epub ahead of print].
  96. Azim HA, Pavlidis N, Peccatori FA. Treatment of the pregnant mother with cancer: a systematic review on the use of cytotoxic, endocrine, targeted agents and immunotherapy during pregnancy. Part II: Hematological tumors. Cancer Treat Rev. 2010; 36(2): 110–121.



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