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Lymphoma

Autologous stem cell transplantation for relapsed/refractory diffuse large B-cell lymphoma: efficacy in the rituximab era and comparison to first allogeneic transplants. A report from the EBMT Lymphoma Working Party

Abstract

In the era of chemoimmunotherapy, the optimal treatment paradigm for relapsed and refractory diffuse large B-cell lymphoma has been challenged. We reviewed the outcome of standard salvage therapy with an autologous stem cell transplant (autoSCT) over the last two decades and the outcome of allogeneic SCT (alloSCT) in the most recent decade. AutoSCT recipients diagnosed between 1992 and 2002 (n=2737) were compared with those diagnosed between 2002 and 2010 (n=3980). Patients diagnosed after 2002 had a significantly lower non-relapse mortality (NRM) and relapse incidence (RI) and a superior PFS and overall survival (OS). A total of 4210 patients diagnosed between 2002 and 2010 underwent either an autoSCT or an alloSCT as their first transplant procedure. Two-hundred and thirty patients received an alloSCT (myeloablative (MACalloSCT) n=132, reduced intensity (RICalloSCT) n=98). The 4-year NRM rates were 7%, 20% and 27% for autoSCT, RICalloSCT and MACalloSCT, respectively. The 4-year RI was 45%, 40% and 38% for autoSCT, RICalloSCT and MACalloSCT, respectively (NS). The 4-year PFS were 48%, 52% and 35% for autoSCT, RICalloSCT and MACalloSCT, respectively. The 4-year OS was 60%, 52% and 38% for autoSCT, RIC alloSCT and MACalloSCT, respectively. After adjustment for confounding factors NRM was significantly worse for patients undergoing alloSCT whilst there was no difference in the RI.

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References

  1. Philip T, Guglielmi C, Hagenbeek A, Somers R, Van Der Lelie H, Bron D et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med 1995; 333: 1540–1545.

    Article  CAS  PubMed  Google Scholar 

  2. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002; 346: 235–242.

    Article  CAS  PubMed  Google Scholar 

  3. Pfreundschuh M, Trumper L, Osterborg A, Pettengell R, Trneny M, Imrie K et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 2006; 7: 379–391.

    Article  CAS  PubMed  Google Scholar 

  4. Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol 2005; 23: 5027–5033.

    Article  CAS  PubMed  Google Scholar 

  5. Gisselbrecht C, Schmitz N, Mounier N, Gingh Gill D, Linch D, Trneny M et al. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20+ diffuse large b-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol 2012; 30: 4462–4469.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT et al. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol 2014; 32: 3490–3496.

    Article  CAS  PubMed  Google Scholar 

  7. Dhedin N, Giraudier S, Gaulard P, Esperou H, Ifrah N, Michalet M et al. Allogeneic bone marrow transplantation in aggressive non-Hodgkin's lymphoma (excluding Burkitt and lymphoblastic lymphoma): a series of 73 patients from the SFGM database. Societ Francaise de Greffe de Moelle. Br J Haematol 1999; 107: 154–161.

    Article  CAS  PubMed  Google Scholar 

  8. Ratanatharathorn V, Uberti J, Karanes C, Abella E, Lum LG, Momin F et al. Prospective comparative trial of autologous versus allogeneic bone marrow transplantation in patients with non-Hodgkin's lymphoma. Blood 1994; 84: 1050–1055.

    CAS  PubMed  Google Scholar 

  9. Doocey RT, Toze CL, Connors JM, Nevill TJ, Gascoyne RD, Barnett MJ et al. Allogeneic haematopoietic stem-cell transplantation for relapsed and refractory aggressive histology non-Hodgkin lymphoma. Br J Haematol 2005; 131: 223–230.

    Article  PubMed  Google Scholar 

  10. Lazarus HM, Zhang MJ, Carreras J, Hayes-Lattin BM, Ataergin AS, Bitran JD et al. A comparison of HLA-identical sibling allogeneic versus autologous transplantation for diffuse large B cell lymphoma: a report from the CIBMTR. Biol Blood Marrow Transplant 2010; 16: 35–45.

    Article  PubMed  Google Scholar 

  11. Bierman PJ, Sweetenham JW, Loberiza FR, Taghipour G, Lazarus HM, Rizzo JD et al. Syngeneic hematopoietic stem-cell transplantation for non-Hodgkin's lymphoma: a comparison with allogeneic and autologous transplantation—The Lymphoma Working Committee of the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation. J Clin Oncol 2003; 21: 3744–3753.

    Article  PubMed  Google Scholar 

  12. Peniket AJ, Ruiz de Elvira MC, Taghipour G, Cordonnier C, Gluckman E, de Witte T et al. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation. Bone Marrow Transplant. 2003; 31: 667–678.

    Article  CAS  PubMed  Google Scholar 

  13. Schimmer AD, Jamal S, Messner H, Keating A, Meharchand J, Huebsch L et al. Allogeneic or autologous bone marrow transplantation (BMT) for non-Hodgkin's lymphoma (NHL): results of a provincial strategy. Ontario BMT Network. Canada. Bone Marrow Transplant 2000; 26: 859–864.

    Article  CAS  PubMed  Google Scholar 

  14. Sirvent A, Dhedin N, Michallet M, Mounier N, Faucher C, Yakoub-Agha I et al. Low nonrelapse mortality and prolonged long-term survival after reduced-intensity allogeneic stem cell transplantation for relapsed or refractory diffuse large B cell lymphoma: report of the SocieteFrancaise de Greffe de Moelle et de TherapieCellulaire. Biol Blood Marrow Transplant 2010; 16: 78–85.

    Article  PubMed  Google Scholar 

  15. Rezvani AR, Norasetthada L, Gooley T, Sorror M, Bouvier ME, Sahebi F et al. Non-myeloablative allogeneic haematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: a multicentre experience. Br J Haematol 2008; 143: 395–403.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Thomson KJ, Morris EC, Bloor A, Cook G, Milligan D, Parker A et al. Favorable long-term survival after reduced-intensity allogeneic transplantation for multiple-relapse aggressive non-Hodgkin's lymphoma. J Clin Oncol 2009; 27: 426–432.

    Article  PubMed  Google Scholar 

  17. Robinson SP, Goldstone AH, Mackinnon S, Carella A, Russell N, Ruiz de Elvira C et al. Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Blood 2002; 100: 4310–4316.

    Article  CAS  PubMed  Google Scholar 

  18. Cole SR, Hernán MA . Adjusted survival curves with inverse probability weights. Comput Methods Programs Biomed 2004; 75: 45–49.

    Article  PubMed  Google Scholar 

  19. Nademanee A, Molina A, Dagis A, Snyder DS, O’Donnell MR, Parker P et al. Autologous stem-cell transplantation for poor-risk and relapsed intermediate- and high-grade non-Hodgkin's lymphoma. Clin Lymphoma 2000; 1: 46–54.

    Article  CAS  PubMed  Google Scholar 

  20. Lerner RE, Thomas W, Defor TE, Weisdorf DJ, Burns LJ . The International Prognostic Index assessed at relapse predicts outcomes of autologous transplantation for diffuse large-cell non-Hodgkin's lymphoma in second complete or partial remission. Biol Blood Marrow Transplant 2007; 13: 486–492.

    Article  PubMed  Google Scholar 

  21. Vose JM, Zhang MJ, Rowlings PA, Lazarus HM, Bolwell BJ, Freytes CO et al. Autologous transplantation for diffuse aggressive non-Hodgkin's lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol 2001; 19: 406–413.

    Article  CAS  PubMed  Google Scholar 

  22. Mournier N, Canals C, Gisselbrecht C, Cornelissen J, Foa R, Conde E et al. High-dose therapy and autologous stem cell transplantation in first relapse for diffuse large B cell lymphoma in the rituximab era: an analysis based on data from the European Blood and Marrow Transplantation Registry. Biol Blood Marrow Transplant 2012; 18: 788–793.

    Article  Google Scholar 

  23. Hamadami M, Parameswaran HN, Zhang Y, Carreras J, Akpek G, Aljurf MD et al. Early failure of front-line Rituximab containing chemoimmunotherapy in diffuse large B cell lymphoma does not predict futility of autologous hematopoietic cell trnsplantation. Biol Blood Marrow Transplant 2014; 20: 1729–1736.

    Article  Google Scholar 

  24. Sorror M, Giralt S, Sandmaier B, De Lima M, Shahjahan M, Maloney DG et al. Hematopoietic cell transplantation-specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission:combined FHCRC and MDACC experiences. Blood 2007; 110: 4606–4613.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. van Kampen RJW, Canals C, Schouten HC, Nagler A, Thomson KJ, Vernant J-P et al. Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell non-Hodgkin's lymphoma relapsing after an autologous stem-cell transplantation: an analysis of the European Group for Blood and Marrow Transplantation Registry. J Clin Oncol 2011; 29: 1342–1348.

    Article  PubMed  Google Scholar 

  26. Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M et al. Rituximab after lymphoma-directed conditioning and allogeneic stem cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomized phase 2 trial. Lancet Oncol 2014; 15: 757–766.

    Article  CAS  PubMed  Google Scholar 

  27. Spaepen K, Stroobants S, Dupont P, Vandenberghe P, Maertens J, Bormans G et al. Prognostic value of pretransplantation positron emission tomography using fluorine 18-fluorodeoxyglucose in patients with aggressive lymphoma treated with high-dose chemotherapy and stem cell transplantation. Blood 2003; 102: 53–59.

    Article  CAS  PubMed  Google Scholar 

  28. Hamlin PA, Zelenetz AD, Kewalramani T, Qin J, Satagopan JM, Verbel D et al. Age-adjusted International Prognostic Index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma. Blood 2003; 102: 1989–1996.

    Article  CAS  PubMed  Google Scholar 

Download references

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Correspondence to S P Robinson.

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Robinson, S., Boumendil, A., Finel, H. et al. Autologous stem cell transplantation for relapsed/refractory diffuse large B-cell lymphoma: efficacy in the rituximab era and comparison to first allogeneic transplants. A report from the EBMT Lymphoma Working Party. Bone Marrow Transplant 51, 365–371 (2016). https://doi.org/10.1038/bmt.2015.286

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