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  • Original Article
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Graft-Versus-Tumor Effects

Autologous transplantation followed closely by reduced-intensity allogeneic transplantation as consolidative immunotherapy in advanced lymphoma patients: a feasibility study

Bone Marrow Transplantation volume 36, pages 443–451 (2005)Cite this article

Summary:

We report outcomes in advanced lymphoma patients (n=32) who enrolled in a trial of prospectively planned combined autologous/reduced-intensity transplantation (RIT) (n=25) or who received RIT shortly after prior autografting because of high relapse risk or progressive disease (n=7). Nine patients on the autologous/RIT transplant protocol did not proceed to planned RIT because of patient choice (n=4), disease progression (n=3), toxicity (n=1), or no adequate donor (n=1). Among the 23 other patients, RIT was started a median of 59 days (range 31–123) after autologous transplant. Fifteen patients had related donors, five patients had unrelated donors, and three patients had cord blood donors. Among all patients completing RIT, the median overall survival time was 385 days (95% CI 272–792), and the median relapse-free survival time was 157 days (95% CI 119–385). At the time of reporting, six patients (26%) remain alive and three patients (13%) remain alive without relapse. The 100-day transplant-related mortality (TRM) was 9% among all patients and was 0% among matched sibling donors. Overall TRM was 43%. Tandem transplant is feasible in advanced lymphoma with low early TRM. However, practical challenges associated with the strategy were significant and high levels of late TRM due to graft-versus-host disease and infections suggest that modifications of the procedure will be needed to improve outcomes and patient retention.

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References

  1. 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.

    Article  CAS  PubMed  Google Scholar 

  2. Philip T, Guglielmi C, Hagenbeek A et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkins lymphoma. N Engl J Med 1995; 333: 1540–1545.

    Article  CAS  PubMed  Google Scholar 

  3. Yuen AR, Rosenberg SA, Hoppe R et al. Comparison between conventional salvage therapy and and high-dose therapy with autografting for recurrent or refractory Hodgkin's disease. Blood 1997; 89: 814–822.

    CAS  PubMed  Google Scholar 

  4. Horwitz SM, Negrin RS, Blume KG et al. Rituximab as adjuvant to high-dose therapy and autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma. Blood 2004; 103: 777–783.

    Article  CAS  PubMed  Google Scholar 

  5. Mangel J, Leitch HA, Connors JM et al. Intensive chemotherapy and autologous stem-cell transplantation plus rituximab is superior to conventional chemotherapy for newly diagnosed advanced stage mantle-cell lymphoma: a matched pair analysis. Ann Oncol 2004; 15: 283–290.

    Article  CAS  PubMed  Google Scholar 

  6. Belhadj K, Delfau-Larue MH, Elgnaoui T et al. Efficiency of in vivo purging with rituximab prior to autologous peripheral blood progenitor cell transplantation in B-cell non-Hodgkin's lymphoma: a single institution study. Ann Oncol 2004; 15: 504–510.

    Article  CAS  PubMed  Google Scholar 

  7. Anderson JE, Litzow MR, Applebaum FR et al. Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin's disease: the 21-year Seattle experience. J Clin Oncol 1993; 11: 2342–2350.

    Article  CAS  PubMed  Google Scholar 

  8. Ratanatharathorn V, Uberti J, Karanes C et al. Prospective comparative trial of autologous versus allogeneic bone marrow transplantation in patients with non-Hodgkin's lymphoma. Blood 1994; 84: 1050–1054.

    CAS  PubMed  Google Scholar 

  9. van Besien KW, Khouri IF, Giralt SA et al. Allogeneic bone marrow transplantation for refractory and recurrent low-grade lymphoma: the case for aggressive management. J Clin Oncol 1995; 13: 1096–1102.

    Article  CAS  PubMed  Google Scholar 

  10. Milpied N, Fielding AK, Pearce RM et al. Allogeneic bone marrow transplant is not better than autologous transplant for patients with relapsed Hodgkin's disease. J Clin Oncol 1996; 14: 1291–1296.

    Article  CAS  PubMed  Google Scholar 

  11. van Besien KW, de Lima M, Giralt SA et al. Management of lymphoma recurrence after allogeneic transplantation: the relevance of graft-versus-lymphoma effect. Bone Marrow Transplant 1997; 19: 977–982.

    Article  CAS  PubMed  Google Scholar 

  12. Peniket AJ, Ruiz de Elvira MC, Taghipour G 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. Giralt S, Estey E, Albitar M et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 1997; 89: 4531–4536.

    CAS  PubMed  Google Scholar 

  14. Khouri IF, Keating M, Körbling M et al. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol 1998; 16: 2817–2824.

    Article  CAS  PubMed  Google Scholar 

  15. Slavin S, Nagler A, Naparstek E et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.

    CAS  PubMed  Google Scholar 

  16. Sykes M, Preffer F, McAfee S et al. Mixed lymphohaemopoietic chimerism and graft-versus-lymphoma effects after non-myeloablative therapy and HLA-mismatched bone-marrow transplantation. Lancet 1999; 353: 1755–1759.

    Article  CAS  PubMed  Google Scholar 

  17. Childs R, Clave E, Contentin N et al. Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses. Blood 1999; 94: 3234–3241.

    CAS  PubMed  Google Scholar 

  18. Kottaridis PD, Milligan DW, Chopra R et al. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood 2000; 96: 2419–2425.

    CAS  PubMed  Google Scholar 

  19. Khouri IF, Saliba RM, Giralt SA et al. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood 2001; 98: 3595–3599.

    Article  CAS  PubMed  Google Scholar 

  20. Alessandrino EP, Bernasconi I, Colombo AA et al. Thiotepa and fludarabine (TT-FLUDA) as conditioning regimen in poor candidates for conventional allogeneic hemopoietic stem cell transplant. Ann Hematol 2001; 80: 521–524.

    Article  CAS  PubMed  Google Scholar 

  21. McSweeney PA, Niederwieser D, Shizuru JA et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97: 3390–3400.

    Article  CAS  PubMed  Google Scholar 

  22. Miller KB, Roberts TF, Chan G et al. A novel reduced intensity regimen for allogeneic hematopoietic stem cell transplantation associated with a reduced incidence of graft-versus-host disease. Bone Marrow Transplant 2004; 33: 881–889.

    Article  CAS  PubMed  Google Scholar 

  23. Jones RJ, Ambinder RF, Piantadosi S et al. Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation. Blood 1991; 77: 649–653.

    CAS  PubMed  Google Scholar 

  24. Schetelig J, Thiede C, Bornhäuser M et al. Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation: The Cooperative German Transplant Study Group. J Clin Oncol 2003; 21: 2747–2753.

    Article  CAS  PubMed  Google Scholar 

  25. Seropian S, Bahceci E, Cooper DL . Allogeneic peripheral blood stem cell transplantation for high-risk non-Hodgkin's lymphoma. Bone Marrow Transplant 2003; 32: 763–769.

    Article  CAS  PubMed  Google Scholar 

  26. Khouri IF, Lee MS, Saliba RM et al. Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol 2003; 21: 4407–4412.

    Article  CAS  PubMed  Google Scholar 

  27. Maloney DG, Molina AJ, Sahebi F et al. Allografting with non-myeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. Blood 2003; 102: 3447–3454.

    Article  CAS  PubMed  Google Scholar 

  28. Carella AM, Cavaliere M, Lerma E et al. Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hematopoietic stem-cell transplantation as treatment of resistant Hodgkin's disease and non-Hodgkin's lymphoma. J Clin Oncol 2000; 18: 3918–3924.

    Article  CAS  PubMed  Google Scholar 

  29. Buser AS, Heim D, Bucher C et al. High-dose chemotherapy using BEAM for tumor debulking without stem cell support followed by early allogeneic reduced intensity conditioning transplantation to induce a graft-versus-lymphoma effect in patients with high risk or refractory lymphoma. Bone Marrow Transplant 2004; 33: 1011–1014.

    Article  CAS  PubMed  Google Scholar 

  30. Nagler A, Or R, Naparstek E et al. Second allogeneic stem cell transplantation using nonmyeloablative conditioning for patients who relapsed or developed secondary malignancies following autologous transplantation. Exp Hematol 2000; 28: 1096–1104.

    Article  CAS  PubMed  Google Scholar 

  31. Nagler A, Slavin S, Varadi G et al. Allogeneic peripheral blood stem cell transplantation using a fludarabine-based low intensity conditioning regimen for malignant lymphoma. Bone Marrow Transplant 2000; 25: 1021–1028.

    Article  CAS  PubMed  Google Scholar 

  32. Wäsch R, Reisser S, Hahn J et al. Rapid achievement of complete donor chimerism and low regimen-related toxicity after reduced conditioning with fludarabine, carmustine, melphalan and allogeneic transplantation. Bone Marrow Transplant 2000; 26: 243–250.

    Article  PubMed  Google Scholar 

  33. Hou JW, Fowler DH, Wilson W et al. Potent graft-versus-lymphoma effect after non-myeloablative stem cell transplant in refractory non-Hodgkin's lymphoma: role of rapid complete donor chimerism (abstract). Blood 2001; 98: 404a.

    Google Scholar 

  34. Spitzer TR, McAfee SL, Dey BR et al. Durable progression free survival (PFS) following non-myeloablative bone marrow transplant (BMT) for chemorefractory diffuse large B cell lymphoma (B-LCL) (abstract). Blood 2001; 98: 672a.

    Google Scholar 

  35. Michallet M, Bilger K, Garbon F et al. Allogeneic hematopoietic stem cell transplantation after nonmyeloablative preparative regimens: impact of pretransplantation and posttransplantation factors on outcome. J Clin Oncol 2001; 19: 3340–3349.

    Article  CAS  PubMed  Google Scholar 

  36. Devine SM, Sanborn R, Jessop E et al. Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem cell transplant. Bone Marrow Transplant 2001; 28: 557–562.

    Article  CAS  PubMed  Google Scholar 

  37. Bertz H, Illerhaus G, Veelken H, Finke J . Allogeneic hematopoetic stem-cell transplantation for patients with relapsed or refractory lymphomas: comparison of high-dose conventional conditioning versus fludarabine-based reduced-intensity regimens. Ann Oncol 2002; 13: 135–139.

    Article  CAS  PubMed  Google Scholar 

  38. Branson K, Chopra R, Kottaridis PD et al. Role of nonmyeloablative allogeneic stem-cell transplantation after failure of autologous transplant in patients with lymphoproliferative malignancies. J Clin Oncol 2002; 20: 4022–4031.

    Article  PubMed  Google Scholar 

  39. Corradini P, Tarella C, Olivieri A et al. Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies. Blood 2002; 99: 75–82.

    Article  CAS  PubMed  Google Scholar 

  40. Robinson SP, Goldstone AH, Mackinnon S et al. Chemoresistant or aggressive lymphoma predicts 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; 15: 4310–4316.

    Article  Google Scholar 

  41. Chakraverty R, Peggs K, Chopra R et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a non-myeloablative conditioning regimen. Blood 2002; 99: 1071–1078.

    Article  CAS  PubMed  Google Scholar 

  42. Martino R, Caballero MD, de la Serna J et al. Low transplant-related mortality after second allogeneic peripheral blood stem cell transplant with reduced-intensity conditioning in adult patients who have failed a prior autologous transplant. Bone Marrow Transplant 2002; 30: 63–68.

    Article  CAS  PubMed  Google Scholar 

  43. Ruiz-Arguelles GJ, Lopez-Martinez B, Lopez-Ariza B . Successful allogeneic stem cell transplantation with nonmyeloablative conditioning in patients with relapsed Hodgkin's disease following autologous stem cell transplantation. Arch Med Res 2003; 34: 242–245.

    Article  PubMed  Google Scholar 

  44. Cooney JP, Stiff PJ, Toor AA, Parthasarathy M . BEAM allogeneic transplantation for patients with Hodgkin's disease who relapse after autologous transplantation is safe and effective. Biol Blood Marrow Transplant 2003; 9: 177–182.

    Article  PubMed  Google Scholar 

  45. Fung HC, Cohen S, Rodriguez R et al. Reduced-intensity allogeneic stem cell transplantation for patients whose prior autologous stem cell transplantation for hematologic malignancy failed. Biol Blood Marrow Transplant 2003; 9: 649–656.

    Article  CAS  PubMed  Google Scholar 

  46. Faulkner RD, Craddock C, Byrne JL et al. BEAM-alemtuzumab reduced intensity allogeneic stem cell transplantation for lymphoproliferative diseases: GVHD, toxicity, and survival in 65 patients. Blood 2004; 103: 428–434.

    Article  CAS  PubMed  Google Scholar 

  47. Escalón MP, Champlin RE, Saliba RM et al. Nonmyeloablative allogeneic hematopoietic transplantation: a promising salvage therapy for patients with non-Hodgkin's lymphoma whose disease has failed a prior autologous transplantation. J Clin Oncol 2004; 22: 2419–2423.

    Article  PubMed  Google Scholar 

  48. Gooley TA, Leisenring W, Crowley J, Storer BE . Estimation of failure probabilities in the presence of competing risks: new representations of old estimations. Stat Med 1999; 18: 695–706.

    Article  CAS  PubMed  Google Scholar 

  49. Snowden JA, Biggs JC, Milliken ST et al. A randomised, blinded, placebo-controlled, dose escalation study of the tolerability and efficacy of filgrastim for haemopoietic stem cell mobilisation in patients with severe active rheumatoid arthritis. Bone Marrow Transplant 1998; 22: 1035–1041.

    Article  CAS  PubMed  Google Scholar 

  50. Burt RK, Fassas A, Snowden J et al. Collection of hematopoietic stem cells from patients with autoimmune diseases. Bone Marrow Transplant 2001; 28: 1–12.

    Article  CAS  PubMed  Google Scholar 

  51. Maris MB, Niederwieser D, Sandmaier BM et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood 2003; 102: 2021–2030.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, and Department of Preventative Medicine and Biometrics, Bone Marrow Transplantation Program, University of Colorado Health Sciences Center, Denver, CO, USA

    J A Gutman, C Zeng & A Baron

  2. Rocky Mountain Cancer Centers, Denver, CO, USA

    S I Bearman & P A McSweeney

  3. Clínica Universitaria de Navarra, Pamplona, Spain

    Y Nieto

  4. University of Arizona Cancer Center, Tucson, AZ, USA

    J W Sweetenham

  5. MD Anderson Cancer Center, Houston, TX, USA

    R B Jones & E J Shpall

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  1. J A Gutman
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Correspondence to J A Gutman.

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Gutman, J., Bearman, S., Nieto, Y. et al. Autologous transplantation followed closely by reduced-intensity allogeneic transplantation as consolidative immunotherapy in advanced lymphoma patients: a feasibility study. Bone Marrow Transplant 36, 443–451 (2005). https://doi.org/10.1038/sj.bmt.1705081

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