The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지

Treatment of Relapsed Hodgkin Lymphoma

재발성 호지킨 림프종의 치료

  • 엄현석 (국립암센터 혈액종양클리닉)
  • Published : 2011.11.01
⟨ Previous Next ⟩

Abstract

Hodgkin lymphoma has been a curable disease, however some patients have relapsed or refractory disease. The standard treatment of these patients is salvage chemotherapy followed by high dose therapy and autologous stem cell transplant (HDT with ASCT) in patients who are chemotherapy-sensitive. Some portion of the patients not eligible for HDT with ASCT because of old age, chemo-refractory and major comorbidities, can be offered alternative approaches such as radiotherapy or conventional chemotherapy. Allogeneic stem cell transplantation could give some benefit in terms of a graft-versus-lymphoma effect. However due to significant toxicity, this approach should be recommended in the context of clinical trials. Biologic markers are served as prognostic markers as well as therapeutic targets. New therapies including novel agents and immune cell therapies are currently being developed. Immune modulatory and immune cell therapies can be effective even in chemo-refractory patients. Efforts should be focused on progression to overcome tumor evasion mechanism and development of better treatment strategies.

Keywords

References

  1. Kuruvilla J. Standard therapy of advanced Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program 2009;497-506.
  2. Won YW, Kwon JH, Lee SI, et al. Clinical features and outcomes of Hodgkin's lymphoma in Korea: Consortium for Improving Survival of Lymphoma (CISL). Ann Hematol 2011, http://dx.doi.org/ 10.1007/s00277-011-1297-x.
  3. Specht L, Gray RG, Clarke MJ, Peto R. Influence of more extensive radiotherapy and adjuvant chemotherapy on long-term outcome of early-stage Hodgkin's disease: a meta-analysis of 23 randomized trials involving 3,888 patients: international Hodgkin's Disease Collaborative Group. J Clin Oncol 1998;16:830-843.
  4. Oza AM, Ganesan TS, Leahy M, et al. Patterns of survival in patients with Hodgkin's disease: long follow up in a single centre. Ann Oncol 1993;4:385-392.
  5. 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;327:1478-1484. https://doi.org/10.1056/NEJM199211193272102
  6. Kuruvilla J, Keating A, Crump M. How I treat relapsed and refractory Hodgkin lymphoma. Blood 2011;117:4208-4217. https://doi.org/10.1182/blood-2010-09-288373
  7. Blum KA. Upcoming diagnostic and therapeutic developments in classical Hodgkin's lymphoma. Hematology Am Soc Hematol Educ Program 2010;2010:93-100. https://doi.org/10.1182/asheducation-2010.1.93
  8. Moskowitz A, Hamlin P, Gerecitano J, et al. Bendamustine is highly active in heavily pre-treated relapsed and refractory Hodgkin lymphoma and serves as a bridge to allogeneic stem cell transplant [Abstract]. Blood 2009;114:A720.
  9. Josting A, Nogova L, Franklin J, et al. Salvage radiotherapy in patients with relapsed and refractory Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Lymphoma Study Group. J Clin Oncol 2005;23:1522-1529. https://doi.org/10.1200/JCO.2005.05.022
  10. Moskowitz CH, 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: 616-623. https://doi.org/10.1182/blood.V97.3.616
  11. 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;341:1051-1054. https://doi.org/10.1016/0140-6736(93)92411-L
  12. 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;359:2065-2071. https://doi.org/10.1016/S0140-6736(02)08938-9
  13. Josting A, Muller H, Borchmann P, et al. Dose intensity of chemotherapy in patients with relapsed Hodgkin's lymphoma. J Clin Oncol 2010;28:5074-5080. https://doi.org/10.1200/JCO.2010.30.5771
  14. Josting A, Rudolph C, Mapara M, et al. 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 2005;16:116-123. https://doi.org/10.1093/annonc/mdi003
  15. 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: Societe Française de Greffe de Moélle. Bone Marrow Transplant 1997; 20:21-26. https://doi.org/10.1038/sj.bmt.1700838
  16. Fung HC, Stiff P, Schriber J, et al. Tandem autologous stem cell transplantation for patients with primary refractory or poor risk recurrent Hodgkin lymphoma. Biol Blood Marrow Transplant 2007;13:594-600. https://doi.org/10.1016/j.bbmt.2007.01.072
  17. Smith SM, van Besien K, Carreras J, et al. Second autologous stem cell transplantation for relapsed lymphoma after a prior autologous transplant. Biol Blood Marrow Transplant 2008;14: 904-912. https://doi.org/10.1016/j.bbmt.2008.05.021
  18. Akpek G, Ambinder RF, Piantadosi S, et al. Long-term results of blood and marrow transplantation for Hodgkin's lymphoma. J Clin Oncol 2001;19:4314-4321.
  19. Gajewski JL, Phillips GL, Sobocinski KA, et al. Bone marrow transplants from HLA-identical siblings in advanced Hodgkin's disease. J Clin Oncol 1996;14:572-578.
  20. Peggs KS, Sureda A, Qian W, et al. Reduced-intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusions on long-term outcomes. Br J Haematol 2007;139:70-80. https://doi.org/10.1111/j.1365-2141.2007.06759.x
  21. 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;26:455-462. https://doi.org/10.1200/JCO.2007.13.2415
  22. Sureda A, Canals C, Arranz R, et al. Allogeneic stem cell transplantation after reduced intensity conditioning (RIC-allo) in patients with relapsed or refractory Hodgkin's lymphoma (HL): final analysis of the HDR-allo protocol- A prospective clinical trial by the Grupo Espanol de Linfomas/Trasplante Autologo de Medula Osea (GEL/TAMO) and the Lymphoma Working Party (LWP) of the European Group for Blood and Marrow Transplantation [Abstract]. Blood 2009;114:A658.
  23. Forero-Torres A, Leonard JP, Younes A, et al. A phase II study of SGN-30 (anti-CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Br J Haematol 2009;146: 171-179. https://doi.org/10.1111/j.1365-2141.2009.07740.x
  24. Fanale M, Fayad L, Pro B, et al. Phase I study of bortezomib in combination with ICE (BICE) in patients with relapsed/refractory classical Hodgkin lymphoma [Abstract]. Blood 2008;112:A3048. https://doi.org/10.1182/blood-2008-02-135715
  25. Georgakis GV, Li Y, Rassidakis GZ, Medeiros LJ, Mills GB, Younes A. Inhibition of the phosphatidylinositol-3 kinase/Akt promotes G1 cell cycle arrest and apoptosis in Hodgkin lymphoma. Br J Haematol 2006;132:503-511.
  26. Johnston PB, Ansell SM, Colgan JP, et al. mTOR inhibition for relapsed or refractory Hodgkin lymphoma: promising single agent activity with everolimus (RAD001) [Abstract]. Blood 2007; 110:A753.
  27. Kirschbaum MH, Goldman BH, Zain JM, et al. Vorinostat (suberoylanilide hydroxamic acid) in relapsed or refractory Hodgkin lymphoma: SWOG 0517 [Abstract]. Blood 2007; 110:A759.
  28. Younes A, Ong TC, Ribrag V, et al. Efficacy of panobinostat in phase II study in patients with relapsed/refractory Hodgkin lymphoma (HL) after high-dose chemotherapy with autologous stem cell transplat [Abstract]. Blood 2009;114:A923.
  29. Younes A, Pro B, Fanale M, et al. Isotype-selective HDAC inhibitor MGCD0103 decreases serum TARC concentrations and produces clinical responses in heavily pretreated patients with relapsed classical Hodgkin lymphoma (HL) [Abstract]. Blood 2007;110:A2566.
  30. Younes A, Pro B, Fayad L. Experience with bortezomib for the treatment of patients with relapsed classical Hodgkin lymphoma. Blood 2006;107:1731-1732. https://doi.org/10.1182/blood-2005-09-3603
  31. Blum KA, Johnson JL, Niedzwiecki D, Canellos GP, Cheson BD, Bartlett NL. Single agent bortezomib in the treatment of relapsed and refractory Hodgkin lymphoma: cancer and leukemia Group B protocol 50206. Leuk Lymphoma 2007;48:1313-1319. https://doi.org/10.1080/10428190701411458
  32. Fanale M, Fayad L, Pro B, et al. Phase I study of bortezomib plus ICE (BICE) for the treatment of relapsed/refractory Hodgkin lymphoma. Br J Haematol 2011;154:284-286. https://doi.org/10.1111/j.1365-2141.2011.08618.x
  33. Kelley TW, Pohlman B, Elson P, Hsi ED. The ratio of FOXP3+ regulatory T cells to granzyme B+ cytotoxic T/NK cells predicts prognosis in classical Hodgkin lymphoma and is independent of bcl-2 and MAL expression. Am J Clin Pathol 2007;128:958-965. https://doi.org/10.1309/NB3947K383DJ0LQ2
  34. Steidl C, Lee T, Shah SP, et al. Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. N Engl J Med 2010;362:875-885. https://doi.org/10.1056/NEJMoa0905680
  35. Kuruvilla J, Taylor D, Wang L, et al. Phase II trial of lenalidomide in patients with relapsed or refractory Hodgkin lymphoma [Abstract]. Blood 2008;112:A3052. https://doi.org/10.1182/blood-2008-06-162768
  36. Jones RJ, Gocke CD, Kasamon YL, et al. Circulating clonotypic B cells in classic Hodgkin lymphoma. Blood 2009;113:5920-5926. https://doi.org/10.1182/blood-2008-11-189688
  37. Younes A, Romaguera J, Hagemeister F, et al. A pilot study of rituximab in patients with recurrent, classic Hodgkin disease. Cancer 2003;98:310-314. https://doi.org/10.1002/cncr.11511
  38. Ambinder RF. Epstein-barr virus and hodgkin lymphoma. Hematology Am Soc Hematol Educ Program 2007;204-209.
  39. Bollard CM, Cooper LJ, Heslop HE. Immunotherapy targeting EBV-expressing lymphoproliferative diseases. Best Pract Res Clin Haematol 2008;21:405-420. https://doi.org/10.1016/j.beha.2008.06.002
  40. Roskrow MA, Rooney CM, Heslop HE, et al. Administration of neomycin resistance gene marked EBV specific cytotoxic T-lymphocytes to patients with relapsed EBV-positive Hodgkin disease. Hum Gene Ther 1998;9:1237-1250. https://doi.org/10.1089/hum.1998.9.8-1237
  41. Bollard CM, Gottschalk S, Leen AM, et al. Complete responses of relapsed lymphoma following genetic modification of tumor-antigenpresenting cells and T-lymphocyte transfer. Blood 2007;110:2838-2845. https://doi.org/10.1182/blood-2007-05-091280
  42. Lucas KG, Salzman D, Garcia A, Sun Q. Adoptive immunotherapy with allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes for recurrent, EBV-positive Hodgkin disease. Cancer 2004;100:1892-1901. https://doi.org/10.1002/cncr.20188