The Role of Autologous and Allogeneic Hematopoietic Stem Cell Transplantation for Hodgkin Lymphoma

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Patients with Hodgkin lymphoma are usually cured by primary therapy using chemotherapy alone or combined modality therapy with external beam radiation. Patients who do not experience a complete remission or those who experience relapse may by salvaged by high-dose therapy and autologous hematopoietic stem cell transplantation (ASCT). Success of this approach is largely dependent on the tumor being sensitive to salvage chemotherapy before transplant. More studies are showing the predictive value of functional imaging in this setting. Allogeneic hematopoietic stem cell transplantation has greater risk of nonrelapse mortality and is generally reserved for patients who experience relapse post-ASCT, but may provide long-term survival for some patients through graft-versus-tumor immune effects.

Correspondence: David G. Maloney, MD, PhD, Clinical Research Division, Transplantation Biology Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue, North, D1-100, Seattle, WA 98104-1029. E-mail: dmaloney@fhcrc.org
  • 1

    BartlettNL. Modern treatment of Hodgkin lymphoma. Curr Opin Hematol2008;15:408-414.

  • 2

    EngertADiehlVFranklinJ. 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 Oncol2009;27:4548-4554.

    • Search Google Scholar
    • Export Citation
  • 3

    MoskowitzAJYahalomJKewalramaniT. Pretransplantation functional imaging predicts outcome following autologous stem cell transplantation for relapsed and refractory Hodgkin lymphoma. Blood2010;116:4934-4937.

    • Search Google Scholar
    • Export Citation
  • 4

    SchmitzNPfistnerBSextroM. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet2002;359:2065-2071.

    • Search Google Scholar
    • Export Citation
  • 5

    SchmitzNHaverkampHJostingA. 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 haemopoetic stem cell transplantation (ASCT) of the German Hodgkin Study Group (GHSG) and the Working Party Lymphoma of the European Group for Blood and Marrow Transplantation (EBMT) [abstract]. J Clin Oncol2005;23(Suppl 16S):Abstract 6508.

    • Search Google Scholar
    • Export Citation
  • 6

    LinchDCWinfieldDGoldstoneAH. Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial. Lancet1993;341:1051-1054.

    • Search Google Scholar
    • Export Citation
  • 7

    PasquiniMCWangZ. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR Summary Slides2010. Available at: http://www.cibmtr.org. Accessed July 26 2011.

    • Search Google Scholar
    • Export Citation
  • 8

    SuredaAConstansMIriondoA. Prognostic factors affecting long-term outcome after stem cell transplantation in Hodgkin's lymphoma autografted after a first relapse. Ann Oncol2005;16:625-633.

    • Search Google Scholar
    • Export Citation
  • 9

    SirohiBCunninghamDPowlesR. Long-term outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma. Ann Oncol2008;19:1312-1319.

    • Search Google Scholar
    • Export Citation
  • 10

    HasencleverDDiehlV. A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. N Engl J Med1998;339:1506-1514.

    • Search Google Scholar
    • Export Citation
  • 11

    ConstansMSuredaATerolMJ. Autologous stem cell transplantation for primary refractory Hodgkin's disease: results and clinical variables affecting outcome. Ann Oncol2003;14:745-751.

    • Search Google Scholar
    • Export Citation
  • 12

    LazarusHMRowlingsPAZhangMJ. Autotransplants for Hodgkin's disease in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol1999;17:534-545.

    • Search Google Scholar
    • Export Citation
  • 13

    SweetenhamJWCarellaAMTaghipourG. High-dose therapy and autologous stem-cell transplantation for adult patients with Hodgkin's disease who do not enter remission after induction chemotherapy: results in 175 patients reported to the European Group for Blood and Marrow Transplantation. Lymphoma Working Party. J Clin Oncol1999;17:3101-3109.

    • Search Google Scholar
    • Export Citation
  • 14

    GopalAKMetcalfeTLGooleyTA. High-dose therapy and autologous stem cell transplantation for chemoresistant Hodgkin lymphoma: the Seattle experience. Cancer2008;113:1344-1350.

    • Search Google Scholar
    • Export Citation
  • 15

    PerskyDOMoskowitzCHFilatovA. High dose chemoradiotherapy and ASCT may overcome the prognostic importance of biologic markers in relapsed/refractory Hodgkin lymphoma. Appl Immunohistochem Mol Morphol2010;18:35-40.

    • Search Google Scholar
    • Export Citation
  • 16

    JostingARuefferUFranklinJ. Prognostic factors and treatment outcome in primary progressive Hodgkin lymphoma: a report from the German Hodgkin Lymphoma Study Group. Blood2000;96:1280-1286.

    • Search Google Scholar
    • Export Citation
  • 17

    VigourouxSMilpiedNAndrieuJM. Front-line high-dose therapy with autologous stem cell transplantation for high risk Hodgkin's disease: comparison with combined-modality therapy. Bone Marrow Transplant2002;29:833-842.

    • Search Google Scholar
    • Export Citation
  • 18

    FedericoMBelleiMBriceP. 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 Oncol2003;21:2320-2325.

    • Search Google Scholar
    • Export Citation
  • 19

    SmithSMvan BesienKCarrerasJ. Second autologous stem cell transplantation for relapsed lymphoma after a prior autologous transplant. Biol Blood Marrow Transplant2008;14:904-912.

    • Search Google Scholar
    • Export Citation
  • 20

    MoskowitzCHYahalomJZelenetzAD. High-dose chemoradiotherapy for relapsed or refractory Hodgkin lymphoma and the significance of pre-transplant functional imaging. Br J Haematol2010;148:890-897.

    • Search Google Scholar
    • Export Citation
  • 21

    SuredaAArranzRIriondoA. 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 Oncol2001;19:1395-1404.

    • Search Google Scholar
    • Export Citation
  • 22

    ForrestDLHoggeDENevillTJ. High-dose therapy and autologous hematopoietic stem-cell transplantation does not increase the risk of second neoplasms for patients with Hodgkin's lymphoma: a comparison of conventional therapy alone versus conventional therapy followed by autologous hematopoietic stem-cell transplantation. J Clin Oncol2005;23:7994-8002.

    • Search Google Scholar
    • Export Citation
  • 23

    FungHCStiffPSchriberJ. Tandem autologous stem cell transplantation for patients with primary refractory or poor risk recurrent Hodgkin lymphoma. Biol Blood Marrow Transplant2007;13:594-600.

    • Search Google Scholar
    • Export Citation
  • 24

    CastagnaLMagagnoliMBalzarottiM. Tandem high-dose chemotherapy and autologous stem cell transplantation in refractory/relapsed Hodgkin's lymphoma: a monocenter prospective study. Am J Hematol2007;82:122-127.

    • Search Google Scholar
    • Export Citation
  • 25

    CzyzJDziadziuszkoRKnopinska-PoslusznyW. Two autologous transplants in the treatment of patients with Hodgkin's lymphoma: analysis of prognostic factors and comparison with a single procedure. Leuk Lymphoma2007;48:535-541.

    • Search Google Scholar
    • Export Citation
  • 26

    MorschhauserFBricePFermeC. Risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation for first relapse/refractory Hodgkin's lymphoma: results of the prospective multicenter H96 trial by the GELA/SFGM study group. J Clin Oncol2008;26:5980-5987.

    • Search Google Scholar
    • Export Citation
  • 27

    NaglerABergerRAckersteinA. A randomized controlled multicenter study comparing recombinant interleukin 2 (rIL-2) in conjunction with recombinant interferon alpha (IFN-alpha) versus no immunotherapy for patients with malignant lymphoma postautologous stem cell transplantation. J Immunother2010;33:326-333.

    • Search Google Scholar
    • Export Citation
  • 28

    BollardCMAguilarLStraathofKC. Cytotoxic T lymphocyte therapy for Epstein-Barr virus+ Hodgkin's disease. J Exp Med2004;200:1623-1633.

  • 29

    SavoldoBRooneyCMDi StasiA. Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30zeta artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease. Blood2007;110:2620-2630.

    • Search Google Scholar
    • Export Citation
  • 30

    YounesABartlettNLLeonardJP. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med2010;363:1812-1821.

  • 31

    ChenRGopalAKSmithSE. Results of a pivotal phase 2 study of brentuximab vedotin (SGN-35) in patients with relapsed or refractory Hodgkin lymphoma [abstract]. Blood2010;116:Abstract 283.

    • Search Google Scholar
    • Export Citation
  • 32

    MilpiedNFieldingAKPearceRM. Allogeneic bone marrow transplant is not better than autologous transplant for patients with relapsed Hodgkin's disease. European Group for Blood and Bone Marrow Transplantation. J Clin Oncol1996;14:1291-1296.

    • Search Google Scholar
    • Export Citation
  • 33

    GajewskiJLPhillipsGLSobocinskiKA. Bone marrow transplants from HLA-identical siblings in advanced Hodgkin's disease. J Clin Oncol1996;14:572-578.

    • Search Google Scholar
    • Export Citation
  • 34

    CooneyJPStiffPJToorAAParthasarathyM. BEAM allogeneic transplantation for patients with Hodgkin's disease who relapse after autologous transplantation is safe and effective. Biol Blood Marrow Transplant2003;9:177-182.

    • Search Google Scholar
    • Export Citation
  • 35

    SuredaARobinsonSCanalsC. 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 Oncol2008;26:455-462.

    • Search Google Scholar
    • Export Citation
  • 36

    KlyuchnikovEBacherUKrogerN. The role of allogeneic stem cell transplantation in relapsed/refractory Hodgkin's Lymphoma patients. Adv Hematol2011;2011:974658.

    • Search Google Scholar
    • Export Citation
  • 37

    RobinsonSPSuredaACanalsC. Reduced intensity conditioning allogeneic stem cell transplantation for Hodgkin's lymphoma: identification of prognostic factors predicting outcome. Haematologica2009;94:230-238.

    • Search Google Scholar
    • Export Citation
  • 38

    SarinaBCastagnaLFarinaLAllogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability. Blood2010;115:3671-3677.

    • Search Google Scholar
    • Export Citation
  • 39

    ThomsonKJPeggsKSSmithP. Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin's lymphoma following autologous stem cell transplantation. Bone Marrow Transplant2008;41:765-770.

    • Search Google Scholar
    • Export Citation
  • 40

    BurroughsLMO'DonnellPVSandmaierBM. Comparison of outcomes of HLA-matched related, unrelated, or HLA-haploidentical related hematopoietic cell transplantation following nonmyeloablative conditioning for relapsed or refractory Hodgkin lymphoma. Biol Blood Marrow Transplant2008;14:1279-1287.

    • Search Google Scholar
    • Export Citation
  • 41

    PeggsKSSuredaAQianW. 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 Haematol2007;139:70-80.

    • Search Google Scholar
    • Export Citation
  • 42

    PeggsKSHunterAChopraR. Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation. Lancet2005;365:1934-1941.

    • Search Google Scholar
    • Export Citation
  • 43

    StiffPJUngerJMFormanSJ. The value of augmented preparative regimens combined with an autologous bone marrow transplant for the management of relapsed or refractory Hodgkin disease: a Southwest Oncology Group phase II trial. Biol Blood Marrow Transpl2003;9:529-539.

    • Search Google Scholar
    • Export Citation
  • 44

    TarellaCCutticaAVitoloU. High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma: a multicenter study of the intergruppo Italiano Linfomi showing prolonged disease free survival in patients treated at first recurrence. Cancer2003;97:2748-2759.

    • Search Google Scholar
    • Export Citation
  • 45

    WadehraNFaragSBolwellB. Long-term outcome of Hodgkin disease patients following high-dose busulfan, etoposide, cyclophosphamide, and autologous stem cell transplantation. Biol Blood Marrow Transplant2006;12:1343-1349.

    • Search Google Scholar
    • Export Citation
  • 46

    CzyzJDziadziuszkoRKnopinska-PostuszuyW. 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 Oncol2004;15:1222-1230.

    • Search Google Scholar
    • Export Citation
  • 47

    EngelhardtBGHollandDWBrandtSJ. High-dose chemotherapy followed by autologous stem cell transplantation for relapsed or refractory Hodgkin lymphoma: prognostic features and outcomes. Leuk Lymphoma2007;48:1728-1735.

    • Search Google Scholar
    • Export Citation
  • 48

    LavoieJCConnorsJMPhillipsGL. High-dose chemotherapy and autologous stem cell transplantation for primary refractory or relapsed Hodgkin lymphoma: long-term outcome in the first 100 patients treated in Vancouver. Blood2005;106:1473-1478.

    • Search Google Scholar
    • Export Citation
  • 49

    AkpekGAmbinderRFPiantadosiS. Long-term results of blood and marrow transplantation for Hodgkin's lymphoma. J Clin Oncol2001;19:4314-4321.

    • Search Google Scholar
    • Export Citation
  • 50

    DevettenMPHariPNCarrerasJ. Unrelated donor reduced-intensity allogeneic hematopoietic stem cell transplantation for relapsed and refractory Hodgkin lymphoma. Biol Blood Marrow Transplant2009;15:109-117.

    • Search Google Scholar
    • Export Citation
  • 51

    AnderliniPSalibaRAcholonuS. Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin's lymphoma: the updated M.D. Anderson Cancer Center experience. Haematologica2008;93:257-264.

    • Search Google Scholar
    • Export Citation
  • 52

    AlvarezISuredaACaballeroMD. Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol. Biol Blood Marrow Transplant2006;12:172-183.

    • Search Google Scholar
    • Export Citation
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