Treatment of very high-risk classical Hodgkin Lymphoma: cases’ selection from real life and critical review of the literature
Keywords:
Hodgking Lymphoma;, high risk HL patien, relapsed/refractory disease, salvage treatmentsAbstract
Over the last 4 decades, advances in radiation therapy and the addition of combination chemotherapy have significantly increased the cure rate of patients with HL, with a 5-year OS of about 90% . However, despite high rate of cure after first line of therapy, 5%-10% of HLs are refractory to the treatment, and 10-30% of patients have a disease relapse after a complete response (CR). Relapsed HL can be treated with salvage therapies with a long-lasting complete remission in 80% of cases. In recent years, novel drugs are available for the patients with relapsed/refractory HL, like Brentuximab Vedotin and immune checkpoint inhibitors. These drugs have been able to rescue a cohort of patients who subsequently could receive an allogeneic stem-cell transplant. Our cases have been chosen because they are representative of critical issues in the management of relapsed/refractory HL; our experiences are consistent with what reported by other Authors.
References
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2. Ansell SM. Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management. Am J Hematol 2018; 93(5):704-15
3. Carella AM, Corradini P, Mussetti A, et al. Treatment of classical Hodgkin lymphoma in the era of brentuximab vedotin and immune checkpoint inhibitors. Annals of Hematology 2018; 97:1301-15
4. 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 forcure. J Clin Oncol 1992;10:210–8.
5. Josting A, Katay 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):289–95
6. 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(8852):1051–4.
7. Shanbhag S, Ambinder RF. Hodgkin lymphoma: A review and update on recent progress. CA Cancer J Clin. 2018;68(2):116-32
8. Evens AM, Helenowski I, Ramsdale E, et al. A retrospective multicenter analysis of elderly Hodgkin lymphoma: outcomes and prognostic factors in the modern era. Blood 2012; 119 (3): 692-5
9. Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD 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.
10. Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood 2016; 128(12): 1562–6.
11. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med 2015 22;372(4):311-9.
12. Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA. Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J Clin Oncol 2017;35(19):2125-32.
13. Moskowitz CH, Walewski J, Nademanee A, Masszi T, Agura E et al. Five-year PFS From the AETHERA Trial of Brentuximab Vedotin for Hodgkin Lymphoma at High Risk of Progression or Relapse. Blood 2018;132(25):2639-42.
14. Zinzani PL, Pellegrini C, Cantonetti M, et al. Brentuximab Vedotin in Transplant-Naïve Relapsed/Refractory Hodgkin Lymphoma: Experience in 30 Patients. Oncologist 2015;20(12):1413-6.
15. Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J et al. 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):1853-62
16. Reyad D, Yassin FK and Bayoumy M. Brentuximab Vedotin in Pretreated Hodgkin Lymphoma Patients: A Systematic Review and Meta-Analysis. Blood 2015; 126:3866
17. Scott LJ. Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma. Drugs 2017;77(4):435-45
18. Brentuximab SmPC
19. Eyre TA, Phillips EH, Linton KM, et al. Results of a multicentre UK-wide retrospective study evaluating the efficacy of brentuximab vedotin in relapsed, refractory classical Hodgkin lymphoma in the transplant naive setting. Br J Haematol 2017;179(3):471-9.
20. Nivolumab SmPC
21. Pembrolizumab SmPC
22. 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):2065–71.
23. Ferme C, Mounier N, Divine M, et al. Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin’s disease in relapse or failure after initial chemotherapy: results of the Groupe d’Etudes des Lymphomes de l’Adulte H89 Trial. J Clin Oncol 2002;20(2):467–75.
24. Moskowitz CH1, Nimer SD, Zelenetz AD, et al. 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 2001; 97(3):616-23.
25. Josting A, Rudolph C, Reiser M, et al. Time-intensified dexamethasone / cisplatin / cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin's disease. Ann Oncol 2002;13(10):1628-35.
26. Santoro A, Magagnoli M, Spina M, et al. Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin's lymphoma. Haematologica 2007;92(1):35-41
27. Santoro A, Mazza R, Pulsoni A, et al. Bendamustine in Combination With Gemcitabine and Vinorelbine Is an Effective Regimen As Induction Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma: Final Results of a Multicenter Phase II Study. J Clin Oncol 2016;34(27):3293-9.
28. Filmont JE, Gisselbrecht C, Cuenca X, et al. The impact of pre- and post-transplantation positron emission tomography using 18-fluorodeoxyglucose on poor-prognosis lymphoma patients undergoing autologous stem cell transplantation. Cancer 2007; 110, 1361–9
29. Castagna L, Bramanti S, Balzarotti M, et al. Predictive value of early 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) during salvage chemotherapy in relapsing/refractory Hodgkin lymphoma (HL) treated with high-dose chemotherapy. Br J Haematol 2009;145(3):369-72.
30. Moskowitz AJ, Yahalom J, Kewalramani T, et al. Pretransplantation functional imaging predicts outcome following autologous stem cell transplantation for relapsed and refractory Hodgkin lymphoma. Blood 2010;116(23):4934-7.
31. Moskowitz CH, Matasar MJ, Zelenetz AD, et al. Normalization of pre-ASCT, FDG-PET imaging with second-line, non-cross-resistant, chemotherapy programs improve event-free survival in patients with Hodgkin lymphoma. Blood 2012;119(7):1665-70.
32. Cavalieri E, Matturro A, Annechini G, et al. Efficacy of the BEACOPP regimen in refractory and relapsed Hodgkin lymphoma. Leuk Lymphoma 2009;50(11):1803-8.
33. Walewski J, Hellmann A, Siritanaratkul N, et al. Prospective study of brentuximab vedotin in relapsed/refractory Hodgkin lymphoma patients who are not suitable for stem cell transplant or multi-agent chemotherapy. Br J Haematol 2018;183(3):400-10.
34. Cole PD, McCarten KM, Pei Q, 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; published online Aug 16. http://dx.doi.org/10.1016/S1470-2045(18)30426-1.
35. Garcia-Sanz R, Sureda A, Gonzalez AP, et al. Brentuximab vedotin plus ESHAP (BRESHAP) is a highly effective combination for inducing remission in refractory and relapsed Hodgkin lymphoma patients prior to autologous stem cell transplant: a trial of the Spanish Group of Lymphoma and Bone Marrow Transplantation (GELTAMO). Blood 2016; 128: 1109.
36. Cassaday RD, Fromm J, Cowan AJ, et al. Safety and activity of brentuximab vedotin (BV) plus ifosfamide, carboplatin, and etoposide (ICE) for rel/ref (rel/ref) classical Hodgkin lymphoma (cHL): initial results of a phase I/II trial. Blood 2016; 128: 1834.
37. Hagenbeek A, Mooij H, Zijlstra J, Lugtenburg P, van Imhoff G, et al. Phase I dose-escalation study of brentuximab-vedotin combined with dexamethasone, high-dose cytarabine and cisplatin, as salvage treatment in relapsed/refractory classical Hodgkin lymphoma: The HOVON/LLPC Transplant BRaVE study. Haematologica 2019; 104: e151-e153.
38. LaCasce A, Bociek G, Sawas A, et al. Brentuximab vedotin plus bendamustine: a highly active salvage treatment regimen for patients with relapsed or refractory Hodgkin lymphoma. Blood 2015; 126: 3982.
39. Herrera AF, Moskowitz AJ, Bartlett NL, et al. Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood 2018; 131: 1183–94.
40. Armand P, Engert A, Younes A, et al. Nivolumab for relapsed/refractory classic Hodgkin Lymphoma after failure of autologous hematopoietic cell transplantation: extended follow‐up of the multicohort single‐arm phase II checkmate 205 trial. J Clin Oncol 2018;36:1428‐39.
41. Beköz H, Karadurmuş N, Paydaş S et al. Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience. Ann Oncol 2017;28(10):2496-2502.
42. Chen R, Zinzani PL, Fanale MA, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory Classic Hodgkin Lymphoma. J Clin Oncol 2017;35(19):2125-32
43. Tucci A, Martelli M, Rigacci L, Riccomagno P, Cabras MG et al. Comprehensive Geriatric Assessment Is an Essential Tool to Support Treatment Decisions in Elderly Patients With Diffuse Large B-cell Lymphoma: A Prospective Multicenter Evaluation in 173 Patients by the Lymphoma Italian Foundation (FIL). Leuk Lymphoma 2015;56(4):921-6.
44. Björkholm M, Weibull CE, Eloranta S, Smedby KE, Glimelius I, Dickman PW. Greater attention should be paid to developing therapies for elderly patients with Hodgkin lymphoma-A population-based study from Sweden. Eur J Haematol 2018;101(1):106-14
45. Abel GA, Klepin HD. Frailty and the management of hematologic malignancies. Blood 2018;131(5):515-24
46. Proctor SJ, Wilkinson J, Jones G, Watson GC, Lucraft HH, Mainou-Fowler T et al. Evaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD study. Blood 2012;119(25):6005-15
47. Forero-Torres A, Holkova B, Goldschmidt J, Chen R, Olsen G, Boccia RV et al. Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older Blood; 126(26): 2798–2804.
48. Evens AM, Advani RH, Helenowski IB, Fanale M, Smith SM, Jovanovic BD. Multicenter Phase II Study of Sequential Brentuximab Vedotin and Doxorubicin, Vinblastine, and Dacarbazine Chemotherapy for Older Patients with Untreated Classical Hodgkin Lymphoma. J Clin Oncol 2018;36(30):3015-22
49. Borchmann S, Engert A, Böll B. Hodgkin lymphoma in elderly patients. Curr Opin Oncol 2018;30(5):308-16
2. Ansell SM. Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management. Am J Hematol 2018; 93(5):704-15
3. Carella AM, Corradini P, Mussetti A, et al. Treatment of classical Hodgkin lymphoma in the era of brentuximab vedotin and immune checkpoint inhibitors. Annals of Hematology 2018; 97:1301-15
4. 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 forcure. J Clin Oncol 1992;10:210–8.
5. Josting A, Katay 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):289–95
6. 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(8852):1051–4.
7. Shanbhag S, Ambinder RF. Hodgkin lymphoma: A review and update on recent progress. CA Cancer J Clin. 2018;68(2):116-32
8. Evens AM, Helenowski I, Ramsdale E, et al. A retrospective multicenter analysis of elderly Hodgkin lymphoma: outcomes and prognostic factors in the modern era. Blood 2012; 119 (3): 692-5
9. Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD 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.
10. Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood 2016; 128(12): 1562–6.
11. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med 2015 22;372(4):311-9.
12. Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA. Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J Clin Oncol 2017;35(19):2125-32.
13. Moskowitz CH, Walewski J, Nademanee A, Masszi T, Agura E et al. Five-year PFS From the AETHERA Trial of Brentuximab Vedotin for Hodgkin Lymphoma at High Risk of Progression or Relapse. Blood 2018;132(25):2639-42.
14. Zinzani PL, Pellegrini C, Cantonetti M, et al. Brentuximab Vedotin in Transplant-Naïve Relapsed/Refractory Hodgkin Lymphoma: Experience in 30 Patients. Oncologist 2015;20(12):1413-6.
15. Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J et al. 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):1853-62
16. Reyad D, Yassin FK and Bayoumy M. Brentuximab Vedotin in Pretreated Hodgkin Lymphoma Patients: A Systematic Review and Meta-Analysis. Blood 2015; 126:3866
17. Scott LJ. Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma. Drugs 2017;77(4):435-45
18. Brentuximab SmPC
19. Eyre TA, Phillips EH, Linton KM, et al. Results of a multicentre UK-wide retrospective study evaluating the efficacy of brentuximab vedotin in relapsed, refractory classical Hodgkin lymphoma in the transplant naive setting. Br J Haematol 2017;179(3):471-9.
20. Nivolumab SmPC
21. Pembrolizumab SmPC
22. 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):2065–71.
23. Ferme C, Mounier N, Divine M, et al. Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin’s disease in relapse or failure after initial chemotherapy: results of the Groupe d’Etudes des Lymphomes de l’Adulte H89 Trial. J Clin Oncol 2002;20(2):467–75.
24. Moskowitz CH1, Nimer SD, Zelenetz AD, et al. 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 2001; 97(3):616-23.
25. Josting A, Rudolph C, Reiser M, et al. Time-intensified dexamethasone / cisplatin / cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin's disease. Ann Oncol 2002;13(10):1628-35.
26. Santoro A, Magagnoli M, Spina M, et al. Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin's lymphoma. Haematologica 2007;92(1):35-41
27. Santoro A, Mazza R, Pulsoni A, et al. Bendamustine in Combination With Gemcitabine and Vinorelbine Is an Effective Regimen As Induction Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma: Final Results of a Multicenter Phase II Study. J Clin Oncol 2016;34(27):3293-9.
28. Filmont JE, Gisselbrecht C, Cuenca X, et al. The impact of pre- and post-transplantation positron emission tomography using 18-fluorodeoxyglucose on poor-prognosis lymphoma patients undergoing autologous stem cell transplantation. Cancer 2007; 110, 1361–9
29. Castagna L, Bramanti S, Balzarotti M, et al. Predictive value of early 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) during salvage chemotherapy in relapsing/refractory Hodgkin lymphoma (HL) treated with high-dose chemotherapy. Br J Haematol 2009;145(3):369-72.
30. Moskowitz AJ, Yahalom J, Kewalramani T, et al. Pretransplantation functional imaging predicts outcome following autologous stem cell transplantation for relapsed and refractory Hodgkin lymphoma. Blood 2010;116(23):4934-7.
31. Moskowitz CH, Matasar MJ, Zelenetz AD, et al. Normalization of pre-ASCT, FDG-PET imaging with second-line, non-cross-resistant, chemotherapy programs improve event-free survival in patients with Hodgkin lymphoma. Blood 2012;119(7):1665-70.
32. Cavalieri E, Matturro A, Annechini G, et al. Efficacy of the BEACOPP regimen in refractory and relapsed Hodgkin lymphoma. Leuk Lymphoma 2009;50(11):1803-8.
33. Walewski J, Hellmann A, Siritanaratkul N, et al. Prospective study of brentuximab vedotin in relapsed/refractory Hodgkin lymphoma patients who are not suitable for stem cell transplant or multi-agent chemotherapy. Br J Haematol 2018;183(3):400-10.
34. Cole PD, McCarten KM, Pei Q, 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; published online Aug 16. http://dx.doi.org/10.1016/S1470-2045(18)30426-1.
35. Garcia-Sanz R, Sureda A, Gonzalez AP, et al. Brentuximab vedotin plus ESHAP (BRESHAP) is a highly effective combination for inducing remission in refractory and relapsed Hodgkin lymphoma patients prior to autologous stem cell transplant: a trial of the Spanish Group of Lymphoma and Bone Marrow Transplantation (GELTAMO). Blood 2016; 128: 1109.
36. Cassaday RD, Fromm J, Cowan AJ, et al. Safety and activity of brentuximab vedotin (BV) plus ifosfamide, carboplatin, and etoposide (ICE) for rel/ref (rel/ref) classical Hodgkin lymphoma (cHL): initial results of a phase I/II trial. Blood 2016; 128: 1834.
37. Hagenbeek A, Mooij H, Zijlstra J, Lugtenburg P, van Imhoff G, et al. Phase I dose-escalation study of brentuximab-vedotin combined with dexamethasone, high-dose cytarabine and cisplatin, as salvage treatment in relapsed/refractory classical Hodgkin lymphoma: The HOVON/LLPC Transplant BRaVE study. Haematologica 2019; 104: e151-e153.
38. LaCasce A, Bociek G, Sawas A, et al. Brentuximab vedotin plus bendamustine: a highly active salvage treatment regimen for patients with relapsed or refractory Hodgkin lymphoma. Blood 2015; 126: 3982.
39. Herrera AF, Moskowitz AJ, Bartlett NL, et al. Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood 2018; 131: 1183–94.
40. Armand P, Engert A, Younes A, et al. Nivolumab for relapsed/refractory classic Hodgkin Lymphoma after failure of autologous hematopoietic cell transplantation: extended follow‐up of the multicohort single‐arm phase II checkmate 205 trial. J Clin Oncol 2018;36:1428‐39.
41. Beköz H, Karadurmuş N, Paydaş S et al. Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience. Ann Oncol 2017;28(10):2496-2502.
42. Chen R, Zinzani PL, Fanale MA, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory Classic Hodgkin Lymphoma. J Clin Oncol 2017;35(19):2125-32
43. Tucci A, Martelli M, Rigacci L, Riccomagno P, Cabras MG et al. Comprehensive Geriatric Assessment Is an Essential Tool to Support Treatment Decisions in Elderly Patients With Diffuse Large B-cell Lymphoma: A Prospective Multicenter Evaluation in 173 Patients by the Lymphoma Italian Foundation (FIL). Leuk Lymphoma 2015;56(4):921-6.
44. Björkholm M, Weibull CE, Eloranta S, Smedby KE, Glimelius I, Dickman PW. Greater attention should be paid to developing therapies for elderly patients with Hodgkin lymphoma-A population-based study from Sweden. Eur J Haematol 2018;101(1):106-14
45. Abel GA, Klepin HD. Frailty and the management of hematologic malignancies. Blood 2018;131(5):515-24
46. Proctor SJ, Wilkinson J, Jones G, Watson GC, Lucraft HH, Mainou-Fowler T et al. Evaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD study. Blood 2012;119(25):6005-15
47. Forero-Torres A, Holkova B, Goldschmidt J, Chen R, Olsen G, Boccia RV et al. Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older Blood; 126(26): 2798–2804.
48. Evens AM, Advani RH, Helenowski IB, Fanale M, Smith SM, Jovanovic BD. Multicenter Phase II Study of Sequential Brentuximab Vedotin and Doxorubicin, Vinblastine, and Dacarbazine Chemotherapy for Older Patients with Untreated Classical Hodgkin Lymphoma. J Clin Oncol 2018;36(30):3015-22
49. Borchmann S, Engert A, Böll B. Hodgkin lymphoma in elderly patients. Curr Opin Oncol 2018;30(5):308-16
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Treatment of very high-risk classical Hodgkin Lymphoma: cases’ selection from real life and critical review of the literature . Acta Biomed [Internet]. 2020 May 25 [cited 2024 Apr. 18];91(S-5):13-22. Available from: https://www.mattioli1885journals.com/index.php/actabiomedica/article/view/9911
