Current Oncology Reports

, Volume 2, Issue 2, pp 182–191 | Cite as

Allogeneic hematopoietic transplantation for chronic lymphocytic leukemia and lymphoma: Potential for nonablative preparative regimens

  • Richard Champlin
  • Koen van Besien
  • Sergio Giralt
  • Issa Khouri


There is increasing interest in the use of allogeneic blood and marrow transplants for chronic lymphocytic leukemia (CLL) and lymphomas. Numerous studies indicate efficacy in patients with advanced disease and demonstrate existence of a potent graft-versus-malignancy effect against these disorders. Allogeneic transplantation is most effective in CLL and low-grade lymphomas, but precise indications and timing of allogeneic transplants in these indolent disorders are not well defined. Allotransplantation is an effective, potentially curative approach, albeit with substantial risks; it is indicated in selected categories of patients. Allogeneic transplants are also promising for mantle cell lymphoma. In large-cell lymphoma, relapses are reduced in allogeneic compared with autologous transplants, but the benefit of allotransplantation has been offset by increased risk of treatment-related complications, and its indications are controversial. A promising new strategy is the use of less toxic, nonmyeloablative preparative regimens to achieve engraftment and allow development of graft-versusmalignancy effects that can produce durable remission in selected categories of lymphoid malignancies.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Harris NL, Jaffe ES, Stein H, et al.: A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994, 84:1361–1392.PubMedGoogle Scholar
  2. 2.
    Dierlamm J, Michaux L, Criel A, et al.: Genetic abnormalities in chronic lymphocytic leukemia and their clinical and prognostic implications. Cancer Genet and Cytogenet 1997, 94:27–35.CrossRefGoogle Scholar
  3. 3.
    Matutes E, Oscier D, Garcia-Marco J, et al.: Trisomy 12 defines a group of CLL with atypical morphology: correlation between cytogenetic, clinical and laboratory features in 544 patients. Br J Haematol 1996, 92:382–388.PubMedCrossRefGoogle Scholar
  4. 4.
    Juliusson G, Oscier DG, Fitchett M, et al.: Prognostic subgroups in B-cell chronic lymphocytic leukemia defined by specific chromosomal abnormalities. N Engl J Med 1990, 323:720–724.PubMedCrossRefGoogle Scholar
  5. 5.
    Arnold A, Cossman J, Bakhshi A, et al.: Immunoglobulin-gene rearrangements as unique clonal markers in human lymphoid malignancies. N Engl J Med 1983, 309:1593–1598.PubMedCrossRefGoogle Scholar
  6. 6.
    Waldmann TA, Davis MM, Bongiovanni KF, Korsmeyer SJ: T cell antigen receptor gene rearrangements serve as markers of lineage and clonality in human lymphoid neoplasms. N Engl J Med 1985, 313:776–783.PubMedCrossRefGoogle Scholar
  7. 7.
    Tkachuk DC, Griesser H, Takihara Y, et al.: Rearrangement of T-cell delta locus in lymphoproliferative disorders. Blood 1988, 72:353–357.PubMedGoogle Scholar
  8. 8.
    Billadeau D, Blackstadt M, Greipp P, et al.: Analysis of B-lymphoid malignancies using allele-specific polymerase chain reaction: a technique for sequential quantitation of residual disease. Blood 1991, 78:3021–3029.PubMedGoogle Scholar
  9. 9.
    Provan D, Bartlett-Pandite L, Zwicky C, et al.: Eradication of polymerase chain reaction-detectable chronic lymphocytic leukemia cells is associated with improved outcome after bone marrow transplantation. Blood 1996, 88:2228–2235.PubMedGoogle Scholar
  10. 10.
    Thomas ED: Bone marrow transplantation for malignant disease. J Clin Oncol 1983, 1:517.PubMedGoogle Scholar
  11. 11.
    Gale RP, Champlin RE: How does bone marrow transplantation cure leukemia? Lancet 1984, 2:28–30.PubMedCrossRefGoogle Scholar
  12. 12.
    Weiden PL, Sullivan KM, Flournoy N, et al., for The Seattle Marrow Transplant Team: Antileukemic effect of chronic graftversus-host disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 1981, 304:1529–1532.PubMedCrossRefGoogle Scholar
  13. 13.
    Horowitz MM, Gale RP, Sondel PM, et al.: Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990, 75:555–562. A comprehensive analysis of clinical evidence supporting graft-versusleukemia effectsPubMedGoogle Scholar
  14. 14.
    Sullivan KM, Storb R, Buckner CD, et al.: Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms. N Engl J Med 1989, 320:828–834.PubMedCrossRefGoogle Scholar
  15. 15.
    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.PubMedCrossRefGoogle Scholar
  16. 16.
    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.PubMedGoogle Scholar
  17. 17.
    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.PubMedGoogle Scholar
  18. 18.
    Mehta J, Powles R, Singhal S, et al.: Clinical and hematologic response of chronic lymphocytic and prolymphocytic leukemia persisting after allogeneic bone marrow transplantation with the onset of acute graft-versus-host disease: possible role of graft-versus-leukemia. Bone Marrow Transplant 1996, 17:371–375.PubMedGoogle Scholar
  19. 19.
    van Besien KW, Khouri IF, Giralt SA, et al.: Allogeneic bone marrow transplantation for refractory and recurrent lowgrade lymphoma: the case for aggressive management. J Clin Oncol 1995, 13:1096–1102.PubMedGoogle Scholar
  20. 20.
    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.PubMedCrossRefGoogle Scholar
  21. 21.
    Rondón G, Giralt S, Huh Y, et al.: Graft-versus-leukemia effect after allogeneic bone marrow transplantation for chronic lymphocytic leukemia. Bone Marrow Transplant 1996, 18:669–672. First report of graft-versus-malignancy in chronic lymphocytic leukemia, a response to donor lymphocyte infusion.PubMedGoogle Scholar
  22. 22.
    Kolb HJ, Schattenberg A, Goldman JM, et al.: Graft-vs-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995, 86:2041–2050. First large-scale comprehensive analysis of donor lymphocyte infusions for induction of graft-versus-malignancy effects.PubMedGoogle Scholar
  23. 23.
    Goulmy E, Voogt P, Van Els C, et al.: The role of minor histocompatibility antigens in GVHD and rejection: a mini-review. Bone Marrow Transplant 1991, 7(suppl 1):49–51.PubMedGoogle Scholar
  24. 24.
    Falkenburg JHF, Goselink HM, Van der Harst D, et al.: Growth inhibition of clonogeneic leukemic precursor cells by minor histocompatibility antigen specific cytotoxic T lymphocytes. J Exp Med 1991, 174:27–33.PubMedCrossRefGoogle Scholar
  25. 25.
    Beatty PG: National heart, lung, and blood institute (NHLBI) workshop on the importance of minor histocompatibility antigens in marrow transplantation. Exper Hematol 1997, 25:548–558.Google Scholar
  26. 26.
    De Beuger M, Bakker A, van Rood JJ, et al.: Tissue distribution of human minor histocompatibility antigens: ubiquitous versus restricted tissue distribution indicates heterogeneity among human cytotoxic T lymphocyte defined non-MHC antigens. J Immunol 1992, 149:1788–1794.Google Scholar
  27. 27.
    Kernan NA, Dupont B: Minor histocompatibility antigens and marrow transplantation. N Engl J Med 1996, 334:323–324.PubMedCrossRefGoogle Scholar
  28. 28.
    Beatty PG: Minor histocompatibility antigens. Exper Hematol 1993, 21:1514–1516.Google Scholar
  29. 29.
    Perreault C, Décary F, Brochu S, et al.: Minor histocompatibility antigens. Blood 1990, 76:1269–1280.PubMedGoogle Scholar
  30. 30.
    Marijt WAF, Veenhof WFJ, Brand A, et al.: Minor histocompatibility antigen-specific cytotoxic T cell lines, capable of lysing human hematopoietic progenitor cells, can be generated in vitro by stimulation with HLA-identical bone marrow cells. J Exp Med 1991, 173:101–109.PubMedCrossRefGoogle Scholar
  31. 31.
    Khouri IF, Keating MJ, Vriesendorp HM, et al.: Autologous and allogeneic bone marrow transplantation for chronic lymphocytic leukemia: preliminary results. J Clin Oncol 1994, 12:748–758.PubMedGoogle Scholar
  32. 32.
    Verdonck LF, Dekker AW, Lokhorst HM, et al.: Allogeneic versus autologous bone marrow transplantation for refractory and recurrent low-grade non-Hodgkin’s lymphoma. Blood 1997, 90:4201–4205.PubMedGoogle Scholar
  33. 33.
    Klingemann HG, Storb R, Fefer A: Bone marrow transplantation in patients aged 45 years and older. Blood 1986, 67:770–776.PubMedGoogle Scholar
  34. 34.
    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.PubMedGoogle Scholar
  35. 35.
    Ringdén O, Horowitz MM, Gale RP, et al.: Outcome after allogeneic bone marrow transplant for leukemia in older adults. JAMA 1993, 270:57–60.PubMedCrossRefGoogle Scholar
  36. 36.
    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.PubMedGoogle Scholar
  37. 37.
    Champlin RE, Gale RP, Foon KA, Golde DW: Chronic leukemias: oncogenes, chromosomes and advances in therapy. Ann Intern Med 1986, 104:671–688.PubMedGoogle Scholar
  38. 38.
    O’Brien S, Del Giglio A, Keating M: Advances in the biology and treatment of B-cell chronic lymphocytic leukemia. Blood 1995, 85:307–318.PubMedGoogle Scholar
  39. 39.
    Foon KA, Rai KR, Gale RP: Chronic lymphocytic leukemia: new insights into biology and therapy. Ann Intern Med 1990, 113:525–539.PubMedGoogle Scholar
  40. 40.
    Jurlander J, Hartmann Geisler C, Hansen MM: Treatment of hypogammaglobulinaemia in chronic lymphocytic leukaemia by low-dose intravenous gammaglobulin. Eur J Haematol 1994, 53:114–118.PubMedCrossRefGoogle Scholar
  41. 41.
    Bunch C: Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia: a randomized, controlled clinical trial. N Engl J Med 1988, 319:902–907.CrossRefGoogle Scholar
  42. 42.
    Lagneaux L, Delforge A, Dorval C, et al.: Excessive production of transforming growth factor-beta by bone marrow stromal cells in B-cell chronic lymphocytic leukemia inhibits growth of hematopoietic precursors and interleukin-6 production. Blood 1993, 82:2379–2385.PubMedGoogle Scholar
  43. 43.
    Binet JL, Catovsky D, Chandra P, et al.: Chronic lymphocytic leukemia: proposals for a revised prognostic staging system. Br J Hematol 1981, 48:365–367.Google Scholar
  44. 44.
    Rai KR, Sawitsky A, Cronkite EP, et al.: Clinical staging of chronic lymphocytic leukemia. Blood 1975, 46:219–234.PubMedGoogle Scholar
  45. 45.
    Rai KR, Han T: Prognostic factors and clinical staging in chronic lymphocytic leukemia. Hematol Oncol Clin North Am 1990, 4:447–456.PubMedGoogle Scholar
  46. 46.
    Cheson BD, Bennett JM, Grever M, et al.: National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996, 87:4990–4997. Guidelines for evaluation and treatment of patients with chronic lymphocytic leukemia.PubMedGoogle Scholar
  47. 47.
    Keating MJ, Kantarjian H, Talpaz M, et al.: Fludarabine: a new agent with major activity against chronic lymphocytic leukemia. Blood 1989, 74:19–25.PubMedGoogle Scholar
  48. 48.
    Keating MJ, O’Brien S, Kantarjian H, et al.: Long-term followup of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent. Blood 1993, 81:2878–2884.PubMedGoogle Scholar
  49. 49.
    O’Brien S, Kantarjian H, Beran M, et al.: Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment. Blood 1993, 82:1695–1700.PubMedGoogle Scholar
  50. 50.
    Keating MJ, Kantarjian H, O’Brien S, et al.: Fludarabine: a new agent with marked cytoreductive activity in untreated chronic lymphocytic leukemia. J Clin Oncol 1991, 9:44–49.PubMedGoogle Scholar
  51. 51.
    Bierman PJ, Vose JM, Anderson JR, et al.: High-dose therapy with autologous hematopoietic rescue for follicular low-grade non-Hodgkin’s lymphoma. J Clin Oncol 1997, 15:445–450.PubMedGoogle Scholar
  52. 52.
    Rabinowe SN, Soiffer RJ, Gribben JG, et al.: Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia. Blood 1993, 82:1366–1376.PubMedGoogle Scholar
  53. 53.
    Traweek ST, Slovak ML, Nademanee AP, et al.: Clonal karyotypic hematopoietic cell abnormalities occurring after autologous bone marrow transplantation for Hodgkin’s disease and non-Hodgkin’s lymphoma. Blood 1994, 84:957–963.PubMedGoogle Scholar
  54. 54.
    Khouri IF, Przepiorka D, van Besien K, et al.: Allogeneic blood or marrow transplantation for chronic lymphocytic leukaemia: timing of transplantation and potential effect of fludarabine on acute graft-versus-host disease. Br J Haematol 1997, 97:466–473.PubMedCrossRefGoogle Scholar
  55. 55.
    Montserrat E, Gale RP, Rozman C: Bone marrow transplants for chronic lymphocytic leukemia. Leukemia 1992, 6:619–622.PubMedGoogle Scholar
  56. 56.
    Michallet M, Archimbaud E, Bandini G, et al.: HLA-identical sibling bone marrow transplantation in younger patients with chronic lymphocytic leukemia. Ann Intern Med 1996, 124:311–315.PubMedGoogle Scholar
  57. 57.
    Croce CM: Molecular biology of lymphomas. Semin Oncol 1993, 20(suppl 5):31–46.PubMedGoogle Scholar
  58. 58.
    Korsmeyer SJ: Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood 1992, 80:879–886.PubMedGoogle Scholar
  59. 59.
    Horning SJ: Natural history of and therapy for the indolent non-Hodgkin’s lymphomas. Semin Oncol 1993, 20(suppl 5):75–88.PubMedGoogle Scholar
  60. 60.
    Romaguera JE, McLaughlin P, North L, et al.: Multivariate analysis of prognostic factors in stage IV follicular low-grade lymphoma: a risk model. J Clin Oncol 1991, 9:762–769.PubMedGoogle Scholar
  61. 61.
    López-Guillermo A, Montserrat E, Bosch F, et al.: Applicability of the International Index for aggressive lymphomas to patients with low-grade lymphoma. J Clin Oncol 1994, 12:1343–1348.PubMedGoogle Scholar
  62. 62.
    Litam P, Swan F, Cabanillas F, et al.: Prognostic value of serum b-2 microglobulin in low-grade lymphoma. Ann Intern Med 1991, 114:855–860.PubMedGoogle Scholar
  63. 63.
    Coiffier B, Bastion Y, Berger F, et al.: Prognostic factors in follicular lymphomas. Semin Oncol 1993, 20(suppl 5):89–95.PubMedGoogle Scholar
  64. 64.
    Portlock CS: Management of the low-grade non-Hodgkin’s lymphomas. Semin Oncol 1990, 17:51–59.PubMedGoogle Scholar
  65. 65.
    Weisdorf DJ, Andersen JW, Glick JH, Oken MM: Survival after relapse of low-grade non-Hodgkin’s lymphoma: implications for marrow transplantation. J Clin Oncol 1992, 10:942–947.PubMedGoogle Scholar
  66. 66.
    Rodriguez MA, Cabanillas FC, Velasquez W, et al.: Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP. J Clin Oncol 1995, 13:1734–1741.PubMedGoogle Scholar
  67. 67.
    McLaughlin P, Hagemeister FB, Romaguera JE, et al.: Fludarabine, mitoxantrone, and dexamethasone: an effective new regimen for indolent lymphoma. J Clin Oncol 1996, 14:1262–1268.PubMedGoogle Scholar
  68. 68.
    Gribben JG, Freedman AS, Neuberg D, et al.: Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma. N Engl J Med 1991, 325:1525–1533.PubMedCrossRefGoogle Scholar
  69. 69.
    Rohatiner AZS, Johnson PWM, Price CGA, et al.: Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for recurrent follicular lymphoma. J Clin Oncol 1994, 12:1177–1184.PubMedGoogle Scholar
  70. 70.
    Negrin RS, Kusnierz-Glaz CR, Still BJ, et al.: Transplantation of enriched and purged peripheral blood progenitor cells from a single apheresis product in patients with non-Hodgkin’s lymphoma. Blood 1995, 85:3334–3341.PubMedGoogle Scholar
  71. 71.
    Johnson PWM, Rohatiner AZS, Whelan JS, et al.: Patterns of survival in patients with recurrent follicular lymphoma: a 20-year study from a single center. J Clin Oncol 1995, 13:140–147.PubMedGoogle Scholar
  72. 72.
    Stone RM, Neuberg D, Soiffer R, et al.: Myelodysplastic syndrome as a late complication following autologous bone marrow transplantation for non-Hodgkin’s lymphoma. J Clin Oncol 1994, 12:2535–2542.PubMedGoogle Scholar
  73. 73.
    Miller JS, Arthur DC, Litz CE, et al.: Myelodysplastic syndrome after autologous bone marrow transplantation: an additional late complication of curative cancer therapy. Blood 1994, 83:3780–3786.PubMedGoogle Scholar
  74. 74.
    Darrington DL, Vose JM, Anderson JR, et al.: Incidence and characterization of secondary myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemoradiotherapy and autologous stem-cell transplantation for lymphoid malignancies. J Clin Oncol 1994, 12:2527–2534.PubMedGoogle Scholar
  75. 75.
    Lundberg JH, Hansen RM, Chitambar CR, et al.: Allogeneic bone marrow transplantation for relapsed and refractory lymphoma using genotypically HLA-identical and alternative donors. J Clin Oncol 1991, 9:1848–1859.PubMedGoogle Scholar
  76. 76.
    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.PubMedCrossRefGoogle Scholar
  77. 77.
    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.PubMedGoogle Scholar
  78. 78.
    van Besien K, Thall P, Korbling M, et al.: Allogeneic transplantation for recurrent or refractory non-Hodgkin’s lymphoma with poor prognostic features after conditioning with thiotepa, busulfan and cyclophosphamide: experience in 44 consecutive patients. Biol Blood and Marrow Transplant 1997, 3:150–156.Google Scholar
  79. 79.
    van Besien K, Sobocinski K, Rowlings PA, et al.: Allogeneic bone marrow transplantation for low-grade lymphoma. Blood 1998, 92:1832–1836. A large International Bone Marrow Transplant Registry analysis of allogeneic bone marrow transplantation for treatment of advanced low-grade lymphoma.PubMedGoogle Scholar
  80. 80.
    Attal M, Socié G, Molina L, et al.: Allogeneic bone marrow transplantation for refractory and recurrent follicular lymphoma: a case-matched analysis with autologous transplantation from the French bone marrow transplant group registry data [abstract]. Blood 1997, 93:1120a.Google Scholar
  81. 81.
    Argatoff LH, Connors JM, Klasa RJ, et al.: Mantle cell lymphoma: a clinicopathologic study of 80 cases. Blood 1997, 89:2067–2078.PubMedGoogle Scholar
  82. 82.
    Hiddemann W, Unterhalt M, Hermann R, et al.: Mantle-cell lymphomas have more widespread disease and a slower response to chemotherapy compared with follicle-center lymphomas: results of a prospective comparative analysis of the German low-grade lymphoma study group. J Clin Oncol 1998, 16:1922–1930.PubMedGoogle Scholar
  83. 83.
    Majlis A, Pugh WC, Rodriguez MA, et al.: Mantle cell lymphoma: correlation of clinical outcome and biologic features with three histologic variants. J Clin Oncol 1997, 15:1664–1671.PubMedGoogle Scholar
  84. 84.
    Freedman AS, Neuberg D, Gribben JG, et al.: High-dose chemoradiotherapy and anti-B-cell monoclonal antibody purged autologous bone marrow transplantation in mantlecell lymphoma: no evidence for long-term remission. J Clin Oncol 1998, 16:13–18.PubMedGoogle Scholar
  85. 85.
    Khouri IF, Romaguera J, Kantarjian H, et al.: Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma. J Clin Oncol 1998, 16:3803–3809.PubMedGoogle Scholar
  86. 86.
    Adkins D, Brown R, Goodnough LT, et al.: Treatment of resistant mantle cell lymphoma with allogeneic bone marrow transplantation. Bone Marrow Transplant 1998, 21:97–99.PubMedCrossRefGoogle Scholar
  87. 87.
    Corradini P, Ladetto M, Astolfi M, et al.: Clinical and molecular remission after allogeneic blood cell transplantation in a patient with mantle-cell lymphoma. Br J Haematol 1996, 94:376–378.PubMedCrossRefGoogle Scholar
  88. 88.
    Khouri I, Romaguera J, Kantarjian H, et al.: Mantle cell lymphoma: improved outcome with hyper-CVAD/high-dose methotrexate-cytarabine (MTX-Ara-C) followed by autologous or allogeneic stem cell transplantation [abstract]. Blood 1997, 90:2642a.Google Scholar
  89. 89.
    Armitage JO: Drug therapy: treatment of non-Hodgkin’s lymphoma. N Engl J Med 1993, 328:1023–1030.PubMedCrossRefGoogle Scholar
  90. 90.
    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.PubMedCrossRefGoogle Scholar
  91. 91.
    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.PubMedCrossRefGoogle Scholar
  92. 92.
    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.PubMedCrossRefGoogle Scholar
  93. 93.
    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.PubMedCrossRefGoogle Scholar
  94. 94.
    Van Besien K, Tabocoff J, Rodriguez M, et al.: High-dose chemotherapy with BEAC regimen and autologous bone marrow transplantation for intermediate grade and immunoblastic lymphoma: durable complete remissions, but a high rate of regimen-related toxicity. Bone Marrow Transplant 1995, 15:549–555.PubMedGoogle Scholar
  95. 95.
    Coiffier B, Gisselbrecht C, Vose JM, et al.: Prognostic factors in aggressive malignant lymphomas: description and validation of a prognostic index that could identify patients requiring a more intensive therapy. J Clin Oncol 1991, 9:211–219.PubMedGoogle Scholar
  96. 96.
    Engelhard M, Brittinger G, Huhn D, et al.: Subclassification of diffuse large B-cell lymphomas according to the Kiel classification: distinction of centroblastic and immunoblastic lymphomas is a significant prognostic risk factor. Blood 1997, 89:2291–2297.PubMedGoogle Scholar
  97. 97.
    Seymour JF, Talpaz M, Cabanillas F, et al.: Serum interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma. J Clin Oncol 1995, 13:575–582.PubMedGoogle Scholar
  98. 98.
    Coiffier B, Lepage E: Prognosis of aggressive lymphomas: a study of five prognostic models with patients included in the LNH-84 regimen. Blood 1989, 74:558–564.PubMedGoogle Scholar
  99. 99.
    Shipp MA: Prognostic factors in aggressive non-Hodgkin’s lymphoma: who has "high-risk" disease. Blood 1994, 83:1165–1173.PubMedGoogle Scholar
  100. 100.
    Rodriguez J, Cabanillas F, McLaughlin P, et al.: A proposal for a simple staging system for intermediate grade lymphoma and immunoblastic lymphoma based on the "tumor score." Ann Oncol 1992, 3:711.PubMedGoogle Scholar
  101. 101.
    The International Non-Hodgkin’s Lymphoma Prognostic Factors Project: A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med 1993, 329:987–995. International index of clinical prognostic factors for predicting outcome of therapy for lymphoma.CrossRefGoogle Scholar
  102. 102.
    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.PubMedGoogle Scholar
  103. 103.
    Blume KG, Long GD, Negrin RS, et al.: Role of etoposide (VP-16) in preparatory regimens for patients with leukemia or lymphoma undergoing allogeneic bone marrow transplantation. Bone Marrow Transplant 1994, 14(suppl 4):9–10.Google Scholar
  104. 104.
    Demirer T, Weaver CH, Buckner CD, et al.: High-dose cyclophosphamide, carmustine, and etoposide followed by allogeneic bone marrow transplantation in patients with lymphoid malignancies who had received prior doselimiting radiation therapy. J Clin Oncol 1995, 13:596–602.PubMedGoogle Scholar
  105. 105.
    Phillips GL, Herzig RH, Lazarus HM, et al.: High-dose chemotherapy, fractionated total-body irradiation, and allogeneic marrow transplantation for malignant lymphoma. J Clin Oncol 1986, 4:480–488.PubMedGoogle Scholar
  106. 106.
    Przepiorka D, Nath R, Ippoliti C, et al.: A Phase I-II study of high-dose thiotepa, busulfan and cyclophosphamide as a preparative regimen for autologous transplantation for malignant lymphoma. Leuk Lymphoma 1995, 17:427–433.PubMedGoogle Scholar
  107. 107.
    de Witte T, Awwad B, Boezeman J, et al.: Role of allogeneic bone marrow transplantation in adolescent or adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma in first remission. Bone Marrow Transplant 1994, 14:767–774.PubMedGoogle Scholar
  108. 108.
    Troussard X, Leblond V, Kuentz M, et al.: Allogeneic bone marrow transplantation in adults with Burkitt’s lymphoma or acute lymphoblastic leukemia in first complete remission. J Clin Oncol 1990, 8:809–812.PubMedGoogle Scholar
  109. 109.
    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. Large case-control study in which allogeneic transplants produced similar survival to autologous transplantation. The lower relapse rate with allogeneic transplantation was offset by a higher rate of treatment-related mortality.PubMedGoogle Scholar
  110. 110.
    Peniket AJ, Ruiz de Elvira MC, Taghipour G, et al.: Allogeneic transplantation for lymphoma produces a lower relapse rate than autologous transplantation but survival has not risen because of higher treatment-related mortality—a report of 764 cases from the EBMT lymphoma registry. Blood 1997, 90:1124a.Google Scholar
  111. 111.
    Bensinger WI, Weaver CH, Appelbaum FR, et al.: Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor. Blood 1995, 85:1655–1658.PubMedGoogle Scholar
  112. 112.
    Korbling M, Przepiorka D, Huh YO, et al.: Allogeneic blood stem cell transplantation for refractory leukemia and lymphoma: potential advantage of blood over marrow allografts. Blood 1995, 85:1659–1665.PubMedGoogle Scholar
  113. 113.
    Przepiorka D, Anderlini P, Ippoliti C, et al.: Allogeneic blood stem cell transplantation in advanced hematologic cancers. Bone Marrow Transplant 1997, 19:455–460.PubMedCrossRefGoogle Scholar
  114. 114.
    Przepiorka D, Ippolitti C, Khouri I, et al.: Allogeneic transplantation for advanced leukemia: improved short-term outcome with blood stem cell grafts and tacrolimus. Transplantation 1996, 62:1806–1810.PubMedCrossRefGoogle Scholar
  115. 115.
    Przepiorka D, Van Besian K, Khouri I, et al.: Etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma. Ann Oncol 1999, 10:527–532.PubMedGoogle Scholar
  116. 116.
    Philip T, Hartman O, Brian P, et al.: High dose therapy and autologous bone marrow transplantation in partial remission after first line induction therapy for diffuse non-Hodgkin’s lymphoma. J Clin Oncol 1988, 8:784–791.Google Scholar
  117. 117.
    Champlin R, Khouri I, Kornblau S, et al.: Allogeneic hematopoietic transplantation as adoptive immunotherapy: induction of graft-vs-malignancy as primary therapy. Hematol Oncol Clin North Am 1999, 13:1041–1057. Summary of concepts of nonablative preparative regimens for allogeneic hematopoietic transplantation.PubMedCrossRefGoogle Scholar
  118. 118.
    Champlin RE, Khouri I, Giralt S: Induction of graft-vs-leukemia as a therapeutic modality. ASCO Education Book 1997, 1:54–58.Google Scholar
  119. 119.
    Champlin RE, Khouri I, Kornblau S, et al.: Reinventing bone marrow transplantation: nonmyeloablative preparative regimens and induction of graft-vs-malignancy effects. Oncology 1999, 3:621–628.Google Scholar
  120. 120.
    Redman JR, Cabanillas F, Velasquez WS, et al.: Phase II trial of fludarabine phosphate in lymphoma: an effective new agent in low-grade lymphoma. J Clin Oncol 1992, 10:790–794.PubMedGoogle Scholar
  121. 121.
    Khouri I, Keating MJ, Przepiorka D, et al.: Engraftment and induction of GVL with fludarabine-based non-ablative preparative regimen in patients with chronic lymphocytic leukemia [abstract]. Blood 1996, 88(suppl 1):301a.Google Scholar
  122. 122.
    Khouri I, Keating M, Korbling M, et al.: Transplant lite: induction of graft-versus-leukemia using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor cell transplantation as treatment for lymphoid malignancies. J Clin Oncol 1998, 16:2817–2824. Initial report of nonmyeloablative hematopoietic transplantation for chronic lymphocytic leukemia and lymphoma.PubMedGoogle Scholar
  123. 123.
    Khouri I, Lee M-S, Palmer L, et al.: Transplant-lite using fludarabine-cyclophosphamide and allogeneic stem cell transplantation for low grade lymphoma [abstract]. Blood 1999, 94:1553a.Google Scholar
  124. 124.
    Mackinnon S, Papadopoulos EB, Carabasi MH, et al.: Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease. Blood 1995, 86:1261–1268.PubMedGoogle Scholar
  125. 125.
    Giralt S, Hester J, Huh Y, et al.: CD8+ depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: graft vs leukemia without graft vs. host disease. Blood 1995, 86:4337–4343.PubMedGoogle Scholar
  126. 126.
    Bonini C, Ferrari G, Verzeletti S, et al.: HSV-TK gene transfer into donor lymphocytes for control of allogeneic graftversus-leukemia. Science 1997, 276:1719–1724.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2000

Authors and Affiliations

  • Richard Champlin
    • 1
  • Koen van Besien
    • 1
  • Sergio Giralt
    • 1
  • Issa Khouri
    • 1
  1. 1.Department of Blood and Marrow TransplantationUniversity of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations