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The Role of Hematopoietic Stem Cell Transplantation in Hodgkin Lymphoma

  • Craig Moskowitz
  • John Sweetenham
Chapter
Part of the Cancer Treatment and Research book series (CTAR, volume 144)

Introduction

Autologous hematopoietic stem cell transplantation (HSCT) has been a standard component of therapy for most patients with relapsed and refractory Hodgkin’s lymphoma (HL; a.k.a. Hodgkin’s disease) for many years. The emergence of new first-line therapies for HL, the application of new staging and imaging techniques and the introduction of nonmyeloablative conditioning for allogeneic HSCT have resulted in a re-evaluation of the role of stem cell transplant strategies in this disease. As first-line therapy continues to improve, the number of patients requiring salvage therapy with HSCT is likely to fall. However, it is likely that this patient population will be particularly challenging, requiring novel salvage approaches.

Autologous HSCT in Hodgkin Lymphoma

Relapsed Disease

The use of conventional-dose salvage therapy for patients with HL who relapse after initial chemotherapy has been disappointing. Studies in patients relapsing after MOPP (mechlorethamine, vincristine,...

Keywords

Overall Survival Hematopoietic Stem Cell Transplantation Allogeneic Hematopoietic Stem Cell Transplantation Autologous Hematopoietic Stem Cell Transplantation Nonmyeloablative Conditioning 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Longo DL, Duffey PL, Young RC, Hubbard SM, Idhe DC, Glatstein E, Phares JC, Jaffe ES, Urba WJ, De Vita VT Jr. Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin’s disease after combination chemotherapy: the low probability of cure. J Clin Oncol. 1992;10:210–8.PubMedGoogle Scholar
  2. 2.
    Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA. Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD or MOPP alternating with ABVD. New Engl J Med. 1992;327:1478–84.PubMedCrossRefGoogle Scholar
  3. 3.
    Horning SJ, Chao NJ, Negrin RS, Hoppe RT, Long GD, Hu WW, Wong RM, Brown BW, Blume KG. High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin’s disease: analysis of the Stanford University results and prognostic indices. Blood 1997;89:801–13.PubMedGoogle Scholar
  4. 4.
    Yuen AR, Rosenberg SA, Hoppe RT, Halpern JD, Horning SJ. Comparison between conventional salvage therapy and high-dose therapy with autografting for recurrent or refractory Hodgkin’s disease. Blood 1997;89:814–22.PubMedGoogle Scholar
  5. 5.
    Reece DE, Connors JM, Spinelli JJ, Barnett MJ, Fairey RN, Klingermann HG, Nantel SH, O’Reilly S, Shepherd JD, Sutherland HJ, Voss N, Chan K-W, Phillips GL. Intensive therapy with cyclophosphamide, carmustine, etoposide ± cisplatin, and autologous bone marrow transplantation for Hodgkin’s disease in first relapse after combination chemotherapy. Blood 1994;83:1193–9.PubMedGoogle Scholar
  6. 6.
    Chopra R, McMillan AK, Linch DC, Yuklea S, Taghipour G, Pearce R, Patterson KG, Goldstone AH. The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin’s disease. A single center eight-year study of 155 patients. Blood 1993;81:1137–45.PubMedGoogle Scholar
  7. 7.
    Sweetenham JW, Taghipour G, Milligan D, Blystad AK, Caballero D, Fassas A, Goldstone AH. High-dose therapy and autologous stem cell rescue for patients with Hodgkin’s disease in first relapse after chemotherapy: results from the EBMT. Bone Marrow Transplant. 1997;20:745–52.PubMedCrossRefGoogle Scholar
  8. 8.
    Linch DC, Winfield D, Goldstone AH, Moir D, Hancock B, McMillan AK, Chopra R, Milligan D, Vaughan-Hudson G. Dose intensification with autologous bone marrow transplantation in relapsed and resistant Hodgkin’s disease: results of a BNLI randomized trial. Lancet 1993;341:1051–4.PubMedCrossRefGoogle Scholar
  9. 9.
    Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M, Boissevain F, Zschaber R, Muller P, Kirchner H, Lohri A, Decker S, Koch B, Hasenclever D, Goldstone AH, Diehl V. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomized trial. Lancet 2002;359:2065–71.PubMedCrossRefGoogle Scholar
  10. 10.
    Schmitz N, Haverkamp H, Josting A, Diehl V, Pfistner B, Carella AM, Haenel N, Biossvain F, Bokemeyer C, Goldstone AH. Long term follow up in relapsed Hodgkin’s disease (HD): updated results of the HD-R1 study comparing conventional chemotherapy (cCT) to high-dose chemotherapy (HDCT) with autologous haemopoietic stem cell transplantation (autologous HSCT) of the German Hodgkin’s Study Group (GHSG) and the Working Party Lymphoma of the European Group for Blood and Marrow Transplantation (EBMT). J Clin Oncol. 2005;23:562s (Abstract).Google Scholar
  11. 11.
    Horning SJ, Hoppe RT, Breslin S, Bartlett NL, Brown BW, Rosenberg SA. Stanford V and radiotherapy for locally extensive and advanced Hodgkin’s disease: mature results of a prospective clinical trial. J Clin Oncol. 2002;20:630–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, Tesch H, Herrmann R, Dorken B, Muller-Hermelink H-K, Duhmke E, Loeffler M. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. New Engl J Med. 2003;348:2386–95.PubMedCrossRefGoogle Scholar
  13. 13.
    Bonfante V, Santoro A, Viviani S, Devizzi L, Balzarotti M, Soncini F, Zanini M, Valagussa P, Bonnadonna G. Outcome of patients with Hodgkin’s disease failing MOPP-ABVD. J Clin Oncol. 1997;15:528–34.PubMedGoogle Scholar
  14. 14.
    Yahalom J, Gulati S, Toia M, Maslak P, McCarron EG, O’Brien JP, Portlock CS, Straus DJ, Phillips J, Fuks Z. Accelerated hyperfractionated total lymphoid irradiation, high-dose chemotherapy and autologous bone marrow transplantation for refractory and relapsing patients with Hodgkin’s disease. J Clin Oncol. 1993;11:1062–70.PubMedGoogle Scholar
  15. 15.
    Moskowitz CH, Kewalramani T, Nimer SD, Gonzalez M, Zelenetz AD, Yaholom J. Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven refractory Hodgkin’s disease. Br J Haematol. 2004;124:645–52.PubMedCrossRefGoogle Scholar
  16. 16.
    Ferme C, Mounier N, Divine M, Brice P, Stamatoullas A, Reman O, Voillat L, Jaubert J, Lederlin P, Colin P, Berger F, Salles G. Intensive salvage therapy with high-dose chemo-radiotherapy 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;20:467–75.PubMedCrossRefGoogle Scholar
  17. 17.
    Constans M, Sureda A, Terol MJ, Arranz R, Caballero MD, Iriondo A, Jarque I, Carreras E, Moraleda JM, Carrera D, Leon A, Lopez A, Albo C, Diaz-Mediavilla J, Fernandez-Abellan P, Garcia-Ruiz JC, Hernandez-Navarro F, Mataix R, Petit J, Pascual MJ, Rifon J, Garcia-Conde J, Fernandez-Ranada JM, Mateos MV, Sierra J, Conde E: GEL/TAMO Cooperative Group. Autologous stem cell transplantation for primary refractory Hodgkin’s disease: results and clinical variables affecting outcome. Ann Oncol. 2003;14:745–51.PubMedCrossRefGoogle Scholar
  18. 18.
    Sweetenham JW, Carella AM, Taghipour G, Cunningham D, Marcus R, Volpe AD, Linch DC, Schmitz N, Goldstone AH. High-dose therapy and autologous stem cell transplantation for adult patients with Hodgkin’s disease who do not enter complete remission after induction chemotherapy: results in 175 patients reported to the European Group for Blood and Marrow Transplantation. J Clin Oncol. 1999;17:3101–9.PubMedGoogle Scholar
  19. 19.
    Lazarus HM, Rowlings PA, Zhang M-J, Vose JM, Armitage JO, Bierman PJ, Gajewski JL, Gale RP, Keating A, Klein JP, Miller CB, Phillips GL, Reece DE, Sobocinski KA, van Beisen K, Horowitz MM. Autotransplants for Hodgkin’s disease in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol. 1999;17:534–45.PubMedGoogle Scholar
  20. 20.
    Josting A, Rueffer U, Franklin J, Seiber M, Diehl V, Engert A. Prognostic factors and treatment outcome in primary progressive Hodgkin lymphoma: a report from the German Hodhkin Lymphoma Study Group. Blood 2000;96:1280–6.PubMedGoogle Scholar
  21. 21.
    Gallamini A, Hutchings M, Rigacci L, Specht L, Merli F, Hansen M, Patti C, Loft A, Di Raimondo F, D’Amore F, Biggi A, Vitolo U, Stelitano C, Sancetta R, Trentin L, Luminari S, Iannitto E, Viviani S, Pierri I, Levis A. Early interim 2-[18F] Fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced Hodgkin’s lymphoma: a report from a joint Italian–Danish study. J Clin Oncol. 2007;25:3746–52.PubMedCrossRefGoogle Scholar
  22. 22.
    Josting A, Rudolph C, Mapara M, Gloosman JP, Sienawski M, Seiber M, Kirchner HH, Dorken B, Hossfiled DK, Kisro J, Metzner B, Berdel WE, Diehl V, Engert A. 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;16:116–23.PubMedCrossRefGoogle Scholar
  23. 23.
    Fung HC, Stiff P, Schriber J, Toor A, Smith E, Rodriguez T, Krishnan A, Molina A, Smith D, Ivers B, Kogut N, Popplewell L, Rodriguez R, Somlo G, Forman SJ, Nademanee A. Tandem autologous stem cell transplantation for patients with primary refractory or poor risk recurrent Hodgkin lymphoma. Biol Blood Marrow Transplant. 2007;13:594–600.PubMedCrossRefGoogle Scholar
  24. 24.
    Moskowitz C. An update on the management of relapsed and primary refractory Hodgkin’s disease. Semin Oncol. 2004;31:54–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Abdel Hamid TM, El Zawahry HM, Khattab NA, Mowafy TM, Awaad MM, Ali El-Din NH, Mokhtar NM. Prognostic factors of Hodgkin’s lymphoma and their impact on response to chemotherapy and survival. J Egypt Natl Canc Inst. 2005;17:9–14.PubMedGoogle Scholar
  26. 26.
    Brice P, Bastion Y, Divine M, Nedellec G, Ferrant A, Gabarre J, Reman O, Lepage A, Ferme C. Analysis of prognostic factors after the first relapse of Hodgkin’s disease in 187 patients. Cancer 1996;78:1293–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Czyz J, Dziadziuszko R, Knopinska-Postuszuy W, Hellmann A, Kachel L, Holowiecki J, Gozdzik J, Hansz J, Avigdor A, Nagler A, Osowiecki M, Walewski J, Mensah P, Jurczak W, Skotnicki A, Sedzimirska M, Lange A, Sawicki W, Sulek K, Wach M, Dmoszynska A, Kus A, Robak T, Warzocha K. Outcome and prognostic factors in advanced Hodgkin’s disease treated with high-dose chemotherapy and autologous stem cell transplantation: a study of 341 patients. Ann Oncol. 2004;15:1222–30.PubMedCrossRefGoogle Scholar
  28. 28.
    Josting A, Engert A, Diehl V, Canellos GP. Prognostic factors and treatment outcome in patients with primary progressive and relapsed Hodgkin’s disease. Ann Oncol. 2002;13 Suppl 1:112–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Sarris AH. Prognostic factors in early-stage Hodgkin’s disease. J Clin Oncol. 1997;15:411–2.PubMedGoogle Scholar
  30. 30.
    Sureda A, Arranz R, Iriondo A, Carreras E, Lahuerta JJ, García-Conde J, Jarque I, Caballero MD, Ferrà C, López A, García-Laraña J, Cabrera R, Carrera D, Ruiz-Romero MD, León A, Rifón J, Díaz-Mediavilla J, Mataix R, Morey M, Moraleda JM, Altés A, López-Guillermo A, de la Serna J, Fernández-Rañada JM, Sierra J, Conde E. Grupo Español de Linformas/Transplante Autólogo de Médula Osea Spanish Cooperative Group. Autologous stem-cell transplantation for Hodgkin’s disease: results and prognostic factors in 494 patients from the Grupo Espanol de Linfomas/Transplante Autologo de Medula Osea Spanish Cooperative Group. J Clin Oncol. 2001;19:395–404.Google Scholar
  31. 31.
    Brice P, Bouabdallah R, Moreau P, Divine M, André M, Aoudjane M, Fleury J, Anglaret B, Baruchel A, Sensebe L, Colombat P. 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 Francaise de Greffe de Moelle. Bone Marrow Transplant. 1997;20:21–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Moskowitz CH, Nimer SD, Zelenetz AD, Trippett T, Hedrick EE, Filippa DA, Louie D, Gonzales M, Walits J, Coady-Lyons N, Qin J, Frank R, Bertino JR, Goy A, Noy A, O’Brien JP, Straus D, Portlock CS, Yahalom J. 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;97:616–23.PubMedCrossRefGoogle Scholar
  33. 33.
    Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V. The international harmonization project on lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25:579–86.PubMedCrossRefGoogle Scholar
  34. 34.
    Sureda A, Constans M, Iriondo A, Arranz R, Caballero MD, Vidal MJ, Petit J, López A, Lahuerta JJ, Carreras E, García-Conde J, García-Laraña J, Cabrera R, Jarque I, Carrera D, García-Ruiz JC, Pascual MJ, Rifón J, Moraleda JM, Pérez-Equiza K, Albó C, Díaz-Mediavilla J, Torres A, Torres P, Besalduch J, Marín J, Mateos MV, Fernández-Rañada JM, Sierra J, Conde E. Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea Cooperative Group. Prognostic factors affecting long-term outcome after stem cell transplantation in Hodgkin’s lymphoma autografted after a first relapse. Ann Oncol. 2005;16:625–33.PubMedCrossRefGoogle Scholar
  35. 35.
    Jabbour E, Hosing C, Ayers G, Nunez R, Anderlini P, Pro B, Khouri I, Younes A, Hagemeister F, Kwak L, Fayad L. Pretransplant positive positron emission tomography/gallium scans predict poor outcome in patients with recurrent/refractory Hodgkin lymphoma. Cancer 2007;109:2481–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Hasenclever D, Diehl V, Armitage JO, Assouline D, Bjorkholm M, Brusamolino E, Canellos GP, Carde P, Crowther D, Cunningham D, Eghbali H, Ferme C, Fisher RI, Glick JH, Glimelius B, Gobbi PG, Holte H, Horning SJ, Lister TA, Longo DL, Mandelli F, Polliak A, Proctor SJ, Specht L, Sweetenham JW, Vaughan-Hudson G. A prognostic score for advanced Hodgkin’s disease. New Engl J Med. 1998;339:1506–14.PubMedCrossRefGoogle Scholar
  37. 37.
    Federico M, Bellei M, Brice P, Brugiatelli M, Nagler A, Gisselbrecht C, Moretti L, Colombat P, Luminari S, Fabbiano F, Di Renzo N, Goldstone A, Carella AM. High-dose therapy and autologous stem cell transplantation versus conventional therapy for patients with advanced Hodgkin’s lymphoma responding to front-line therapy. J Clin Oncol. 2003;21:2320–5.PubMedCrossRefGoogle Scholar
  38. 38.
    Milpied N, Fielding AK, Pearce R, Ernst P, Goldstone AH. Allogeneic bone marrow transplant is not better than autologous transplant for patients with relapsed Hodgkin’s disease. J Clin Oncol. 1996;14:1291–6.PubMedGoogle Scholar
  39. 39.
    Gajewski JL, Phillips GL, Sobconski KA, Armitage JO, Gale RP, Champlin RE, Herzig RH, Hurd DD, Jagannath S, Lkein JP, Lazarus HM, McCarthy PL, Pavlovsky S, Peterson FB, Rowlings PA, Russell JA, Silver SM, Vose JM, Wiernik PH, Bortin MM, Horowitz MM. Bone marrow transplants from HLA-identical siblings in advanced Hodgkin’s disease. J Clin Oncol. 1996;14:572–8.PubMedGoogle Scholar
  40. 40.
    Anderson JE, Litzow MR, Appelbaum FR, Schoch G, Fisher LD, Buckner CD, Peterson FB, Crawford SW, Press OW, Sanders JE. Allogeneic syngeneic and autologous marrow transplantation for Hodgkin’s disease: the 21-year Seattle experience. J Clin Oncol. 1993;11:2342–50.PubMedGoogle Scholar
  41. 41.
    Akpek G, Ambinder RF, Piantodosi S, Abrams RA, Brodsky RA, Vogelsang GB, Zahurak ML, Fuller D, Miller CB, Noga SJ, Fuchs E, Flinn IW, O’Donnell P, Seifter EJ, Mann RB, Jones RJ. Long-term results of blood and marrow transplantation for Hodgkin’s lymphoma. J Clin Oncol. 2001;19:4314–21.PubMedGoogle Scholar
  42. 42.
    Anderlini P, Saliba R, Acholonu S, Okoroji GJ, Donato M, Giralt S, Andersson B, Ueno NT, Khouri I, De Lima M, Hosing C, Cohen A, Ippoliti C, Romaguera J, Rodriguez MA, Pro B, Fayad L, Goy A, Younes A, Champlin RE. Reduced-intensity allogeneic stem cell transplantation in relapsed and refractory Hodgkin’s disease: low transplant-related mortality and impact of intensity of conditioning regimen. Bone Marrow Transplant. 2005;35:945–51.CrossRefGoogle Scholar
  43. 43.
    Burroughs LM, Maris MB, Sandmeier BM. HLA-matched related (MRD) or unrelated donor (MUD) nonmyeloablative conditioning and hematopoietic cell transplant (HCT) for patients with advanced Hodgkin’s disease (HD). Biol Blood Marrow Transplant. 2005;10 Suppl 1:73–4.Google Scholar
  44. 44.
    Alvarez I, Sureda A, Caballero MD, Urbano-Ispizua A, Ribera JM, Canales M, García-Conde J, Sanz G, Arranz R, Bernal MT, de la Serna J, Díez JL, Moraleda JM, Rubió-Félix D, Xicoy B, Martínez C, Mateos MV, Sierra J. Non-myeloablative stem cell transplantation is an effective therapy for refractory or relapsed Hodgkin’s lymphoma: results of a Spanish prospective cooperative protocol. Biol Blood Marrow Transplant. 2006;12:172–83.PubMedCrossRefGoogle Scholar
  45. 45.
    Peggs KS, Hunter A, Chopra R, Parker A, Mahendra P, Milligan D, Craddock C, Pettengell R, Dogan A, Thomson KJ, Morris EC, Hale G, Waldmann H, Goldstone AH, Linch DC, Mackinnon S. Clinical evidence of a graft-versus-Hodgkin’s-lymphoma effect after reduced-intensity allogeneic transplantation. Lancet 2005;365:1934–41.PubMedCrossRefGoogle Scholar
  46. 46.
    Sureda A, Robinson S, Canals C, Carella AM, Boogaerts MA, Caballero D, Hunter AE, Kanz L, Slavin S, Cornelissen JJ, Gramatzki M, Niederwieser D, Russell NH, Schmitz N. 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;26:455–62.Google Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Memorial Sloan-Kettering Cancer CenterNew YorkUSA

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