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Why aren't we performing more allografts for aggressive non-Hodgkin's lymphoma?

Summary:

Allogeneic stem cell transplantation has an under-appreciated role in the management of intermediate-grade non-Hodgkin's lymphoma. It provides several advantages over autologous stem cell transplantation including provision of a lymphoma-free graft, reduced rates of secondary myelodysplastic syndrome and leukemia, and a potentially curative graft-versus-lymphoma effect. When applied to chemosensitive patients, the lower relapse rates and reasonable long-term outcomes make allogeneic transplantation a promising therapy to pursue. Patient populations, such as those with bone marrow involvement or very high-risk disease, can be identified as having suboptimal outcomes after autotransplantation and may benefit from such an approach. While the exact role of allogeneic stem cell transplantation remains to be determined, broad recommendations can be suggested for the management of patients with intermediate-grade lymphoma. New approaches to allogeneic transplantation, including the use of matched-unrelated donors and reduced-intensity conditioning regimens, may expand the applicability of this potentially curative modality.

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References

  1. Garber K . Lymphoma rate rise continues to baffle researchers. J Natl Cancer Inst 2001; 93: 494–496.

    Article  CAS  PubMed  Google Scholar 

  2. Fisher RI, Gaynor ER, Dahlberg S et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med 1993; 328: 1002–1006.

    Article  CAS  PubMed  Google Scholar 

  3. Gordon LI, Harrington D, Andersen J et al. Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma. N Engl J Med 1992; 327: 1342–1349.

    Article  CAS  PubMed  Google Scholar 

  4. Philip T, Guglielmi C, Hagenbeek A 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 

  5. Hahn T, Wolff SN, Czuczman M et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of diffuse large cell B-cell non- Hodgkin's lymphoma: an evidence-based review. Biol Blood Marrow Transplant 2001; 7: 308–331.

    Article  CAS  PubMed  Google Scholar 

  6. Vose JM, Rizzo JD, Wu JT et al. Autotransplantation for non-Hodgkin's lymphoma in 1st relapse or 2nd complete remission: prognostic factor analysis. Blood 2000; 96: 481a.

    Google Scholar 

  7. Santini G, Salvagno L, Leoni P et al. VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group. J Clin Oncol 1998; 16: 2796–2802.

    Article  CAS  PubMed  Google Scholar 

  8. Gianni AM, Bregni M, Siena S et al. High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med 1997; 336: 1290–1297.

    Article  CAS  PubMed  Google Scholar 

  9. Haioun C, Lepage E, Gisselbrecht C et al. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol--a groupe d'Etude des lymphomes de l'Adulte study. J Clin Oncol 2000; 18: 3025–3030.

    Article  CAS  PubMed  Google Scholar 

  10. Kaiser U, Uebelacker I, Abel U et al. Randomized study to evaluate the use of high-dose therapy as part of primary treatment for ‘aggressive’ lymphoma. J Clin Oncol 2002; 20: 4413–4419.

    Article  CAS  PubMed  Google Scholar 

  11. Kluin-Nelemans HC, Zagonel V, Anastasopoulou A et al. Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin's lymphoma: randomized phase III EORTC study. J Natl Cancer Inst 2001; 93: 22–30.

    Article  CAS  PubMed  Google Scholar 

  12. Milpied N, Deconninck E, Colombat P et al. Frontline high-dose chemotherapy (HDC) with autologous stem cell tranplantation vs standard CHOP regimen for patients (⩽60 years) with non IPI high-risk intermediate or high grade lymphomas (NHL). Final results of a randomized trial by the GOELAMS. Ann Oncol 2002; 13 (Suppl. 2): 28a.

    Google Scholar 

  13. Linch DC, Yung L, Smith P et al. A randomized trial of CHOP × 6-8 vs CHOP × 3 + ASCT in 457 patients with poor prognosis histologically aggressive non-Hodgkins lymphoma. Ann Oncol 2002; 13 (Suppl. 2): 28a.

    Google Scholar 

  14. van Besien K, Sobocinski KA, Rowlings PA et al. Allogeneic bone marrow transplantation for low-grade lymphoma. Blood 1998; 92: 1832–1836.

    CAS  PubMed  Google Scholar 

  15. Horowitz MM, Gale RP, Sondel PM et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  PubMed  Google Scholar 

  16. Collins Jr RH, Shpilberg O, Drobyski WR et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1997; 15: 433–444.

    Article  PubMed  Google Scholar 

  17. 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 

  18. van Besien KW, Mehra RC, Giralt SA et al. Allogeneic bone marrow transplantation for poor-prognosis lymphoma: response, toxicity and survival depend on disease histology. Am J Med 1996; 100: 299–307.

    Article  CAS  PubMed  Google Scholar 

  19. Dhedin N, Giraudier S, Gaulard P 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 

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

    CAS  PubMed  Google Scholar 

  21. Nachbaur D, Oberaigner W, Fritsch E et al. Allogeneic or autologous stem cell transplantation (SCT) for relapsed and refractory Hodgkin's disease and non-Hodgkin's lymphoma: a single- centre experience. Eur J Haematol 2001; 66: 43–49.

    Article  CAS  PubMed  Google Scholar 

  22. Chopra R, Goldstone AH, Pearce R et al. Autologous versus allogeneic bone marrow transplantation for non-Hodgkin's lymphoma: a case-controlled analysis of the European Bone Marrow Transplant Group Registry data. J Clin Oncol 1992; 10: 1690–1695.

    Article  CAS  PubMed  Google Scholar 

  23. 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: 1050–1055.

    CAS  PubMed  Google Scholar 

  24. Mendoza E, Territo M, Schiller G et al. Allogeneic bone marrow transplantation for Hodgkin's and non-Hodgkin's lymphoma. Bone Marrow Transplant 1995; 15: 299–303.

    CAS  PubMed  Google Scholar 

  25. Mitterbauer M, Neumeister P, Kalhs P et al. Long-term clinical and molecular remission after allogeneic stem cell transplantation (SCT) in patients with poor prognosis non-Hodgkin's lymphoma. Leukemia 2001; 15: 635–641.

    Article  CAS  PubMed  Google Scholar 

  26. Soiffer RJ, Freedman AS, Neuberg D et al. CD6+ T cell-depleted allogeneic bone marrow transplantation for non- Hodgkin's lymphoma. Bone Marrow Transplant 1998; 21: 1177–1181.

    Article  CAS  PubMed  Google Scholar 

  27. Juckett M, Rowlings P, Hessner M et al. T cell-depleted allogeneic bone marrow transplantation for high-risk non-Hodgkin's lymphoma: clinical and molecular follow-up. Bone Marrow Transplant 1998; 21: 893–899.

    Article  CAS  PubMed  Google Scholar 

  28. Bierman PJ, Sweetenham J, Loberiza F et al. Syngeneic hematopoietic stem cell transplantation for non-Hodgkin's lymphoma (NHL): Comparison with allogeneic and autologous transplants suggests a role for purging. Proc Am Soc Clin Oncol 2001; 20 (Suppl. 1): 5a.

    Google Scholar 

  29. Bierman PJ . Allogeneic bone marrow transplantation for lymphoma. Blood Rev 2000; 14: 1–13.

    Article  CAS  PubMed  Google Scholar 

  30. 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 

  31. Toze CL, Conneally EA, Connors JM et al. Allogeneic hematopoietic stem cell transplantation (AlloHSCT) for non-Hodgkin's lymphoma (NHL) in Vancouver: 17-year experience of the Leukemia? BMT Program of British Columbia (BC) with related donor (RD) and unrelated (UD) donors. Ann Oncol 2002; 13 (Suppl. 2): 39a.

    Google Scholar 

  32. Kiss TL, Abdolell M, Jamal N et al. Long-term medical outcomes and quality-of-life assessment of patients with chronic myeloid leukemia followed at least 10 years after allogeneic bone marrow transplantation. J Clin Oncol 2002; 20: 2334–2343.

    Article  CAS  PubMed  Google Scholar 

  33. Pedersen-Bjergaard J, Andersen MK, Christiansen DH . Therapy-related acute myeloid leukemia and myelodysplasia after high-dose chemotherapy and autologous stem cell transplantation. Blood 2000; 95: 3273–3279.

    CAS  PubMed  Google Scholar 

  34. Sharp JG, Kessinger A, Mann S et al. Outcome of high-dose therapy and autologous transplantation in non- Hodgkin's lymphoma based on the presence of tumor in the marrow or infused hematopoietic harvest. J Clin Oncol 1996; 14: 214–219.

    Article  CAS  PubMed  Google Scholar 

  35. Demirkazik A, Kessinger A, Armitage JO et al. Progenitor and lymphoma cells in blood stem cell harvests: impact on survival following transplantation. Bone Marrow Transplant 2001; 28: 207–212.

    Article  CAS  PubMed  Google Scholar 

  36. Sharp JG, Joshi SS, Armitage JO et al. Significance of detection of occult non-Hodgkin's lymphoma in histologically uninvolved bone marrow by a culture technique. Blood 1992; 79: 1074–1080.

    CAS  PubMed  Google Scholar 

  37. Jacquy C, Soree A, Lambert F et al. A quantitative study of peripheral blood stem cell contamination in diffuse large-cell non-Hodgkin's lymphoma: one-half of patients significantly mobilize malignant cells. Br J Haematol 2000; 110: 631–637.

    Article  CAS  PubMed  Google Scholar 

  38. Appelbaum FR, Sullivan KM, Buckner CD et al. Treatment of malignant lymphoma in 100 patients with chemotherapy, total body irradiation, and marrow transplantation. J Clin Oncol 1987; 5: 1340–1347.

    Article  CAS  PubMed  Google Scholar 

  39. van Dam FS, Schagen SB, Muller MJ et al. Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: high-dose versus standard-dose chemotherapy. J Natl Cancer Inst 1998; 90: 210–218.

    Article  CAS  PubMed  Google Scholar 

  40. Waters TM, Bennett CL, Pajeau TS et al. Economic analyses of bone marrow and blood stem cell transplantation for leukemias and lymphoma: what do we know? Bone Marrow Transplant 1998; 21: 641–650.

    Article  CAS  PubMed  Google Scholar 

  41. Stein RS, Greer JP, Goodman S et al. Intensified preparative regimens and allogeneic transplantation in refractory or relapsed intermediate and high grade non-Hodgkin's lymphoma. Leukemia Lymphoma 2001; 41: 343–352.

    Article  CAS  PubMed  Google Scholar 

  42. Peniket AJ, Ruiz de Elvira MC, Taghipour G et al. Allogeneic transplantation for lymphoma produces a lower relapse rate than autologous transplantation but survival is worse because of higher treatment related mortality — a report of 764 cases from the EBMT lymphoma registry. Blood 1997; 90 (10 Suppl. 1): 255a.

    Google Scholar 

  43. Schimmer AD, Jamal S, Messner H 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 

  44. Dann EJ, Daugherty CK, Larson RA . Allogeneic bone marrow transplantation for relapsed and refractory Hodgkin's disease and non-Hodgkin's lymphoma. Bone Marrow Transplant 1997; 20: 369–374.

    Article  CAS  PubMed  Google Scholar 

  45. Shepherd JD, Barnett MJ, Connors JM et al. Allogeneic bone marrow transplantation for poor-prognosis non-Hodgkin's lymphoma. Bone Marrow Transplant 1993; 12: 591–596.

    CAS  PubMed  Google Scholar 

  46. Philip T, Armitage JO, Spitzer G et al. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med 1987; 316: 1493–1498.

    Article  CAS  PubMed  Google Scholar 

  47. Petersen FB, Appelbaum FR, Hill R et al. Autologous marrow transplantation for malignant lymphoma: a report of 101 cases from Seattle. J Clin Oncol 1990; 8: 638–647.

    Article  CAS  PubMed  Google Scholar 

  48. Vose JM, Anderson JR, Kessinger A et al. High-dose chemotherapy and autologous hematopoietic stem-cell transplantation for aggressive non-Hodgkin's lymphoma. J Clin Oncol 1993; 11: 1846–1851.

    Article  CAS  PubMed  Google Scholar 

  49. Mills W, Chopra R, McMillan A et al. BEAM chemotherapy and autologous bone marrow transplantation for patients with relapsed or refractory non-Hodgkin's lymphoma. J Clin Oncol 1995; 13: 588–595.

    Article  CAS  PubMed  Google Scholar 

  50. Vose JM, Zhang MJ, Rowlings PA 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 

  51. Stiff PJ, Dahlberg S, Forman SJ et al. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens—a Southwest Oncology Group trial. J Clin Oncol 1998; 16: 48–55.

    Article  CAS  PubMed  Google Scholar 

  52. Kewalramani T, Zelenetz AD, Hedrick EE et al. High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis. Blood 2000; 96: 2399–2404.

    CAS  PubMed  Google Scholar 

  53. de Lima M, van Besien KW, Giralt SA et al. Bone marrow transplantation after failure of autologous transplant for non-Hodgkin's lymphoma. Bone Marrow Transplant 1997; 19: 121–127.

    Article  CAS  PubMed  Google Scholar 

  54. Tsai T, Goodman S, Saez R et al. Allogeneic bone marrow transplantation in patients who relapse after autologous transplantation. Bone Marrow Transplant 1997; 20: 859–863.

    Article  CAS  PubMed  Google Scholar 

  55. Vandenberghe E, Pearce R, Taghipour G et al. Role of a second transplant in the management of poor-prognosis lymphomas: a report from the European Blood and Bone Marrow Registry. J Clin Oncol 1997; 15: 1595–1600.

    Article  CAS  PubMed  Google Scholar 

  56. Kusnierz-Glaz CR, Schlegel PG, Wong RM et al. Influence of age on the outcome of 500 autologous bone marrow transplant procedures for hematologic malignancies. J Clin Oncol 1997; 15: 18–25.

    Article  CAS  PubMed  Google Scholar 

  57. Miller CB, Piantadosi S, Vogelsang GB et al. Impact of age on outcome of patients with cancer undergoing autologous bone marrow transplant. J Clin Oncol 1996; 14: 1327–1332.

    Article  CAS  PubMed  Google Scholar 

  58. Rapoport AP, DiPersio JF, Martin BA et al. Patients age 40 years undergoing autologous or allogeneic BMT have regimen-related mortality rates and event-free survivals comparable to patients <40 years. Bone Marrow Transplant 1995; 15: 523–530.

    CAS  PubMed  Google Scholar 

  59. Frassoni F, Labopin M, Gluckman E et al. Results of allogeneic bone marrow transplantation for acute leukemia have improved in Europe with time—a report of the acute leukemia working party of the European group for blood and marrow transplantation (EBMT). Bone Marrow Transplant 1996; 17: 13–18.

    CAS  PubMed  Google Scholar 

  60. Popplewell LL, Forman SJ . Is there an upper age limit for bone marrow transplantation? Bone Marrow Transplant 2002; 29: 277–284.

    Article  CAS  PubMed  Google Scholar 

  61. Bierman P, Molina A, Nelson G et al. Matched unrelated donor (MUD) allogeneic bone marrow transplantation for non-Hodgkin's lymphoma: results from the National Marrow Donor Program (NMDP). Proc Am Soc Clin Oncol 1999; 18: 3a.

    Google Scholar 

  62. Singer CR, Taghipour G, Boogaerts MA et al. Matched unrelated donor (MUD) bone marrow transplantation for adults and children with non-Hodgkin's lymphoma and Hodgkin's lymphoma: preliminary analysis of 56 cases reported to EBMT lymphoma registry. Blood 1999; 94 (Suppl. 1): 560a.

    Google Scholar 

  63. Khouri IF, Saliba RM, Lee M-S et al. Nonablative allogeneic stem cell transplantation (AST) for non-Hodgkin's lymphoma (NHL): improved outcome with low incidence of acute GVHD and treatment related mortality. Blood 2001; 98 (Suppl. 1): 416a.

    Google Scholar 

  64. Spitzer TR, McAfee SL, Dey BR et al. Durable progression free survival (PFS) following non-myeloablative bone marrow transplantation (BMT) for chemorefractory diffuse large B cell clymphoma (B-LCL). Blood 2001; 98 (11 Suppl. 1): 672a.

    Google Scholar 

  65. Kyriakou CA, Milligan D, Chopra R et al. Outcome of non-myeloablative stem cell transplantation for NHL is dependent on histology: good for patients with low grade disease and poor for those with high grade lymphoma. Blood 2001; 98 (Suppl. 1): 414a.

    Google Scholar 

  66. Robinson SP, Goldstone AH, Mackinnon S 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 

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Mollee, P., Lazarus, H. & Lipton, J. Why aren't we performing more allografts for aggressive non-Hodgkin's lymphoma?. Bone Marrow Transplant 31, 953–960 (2003). https://doi.org/10.1038/sj.bmt.1704040

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