T-cell depletion for bone marrow transplantation: Effects on graft rejection, graft-versus-host disease, graft-versus-leukemia, and survival

  • Richard E. Champlin
Part of the Cancer Treatment and Research book series (CTAR, volume 50)

Abstract

Graft-versus-host disease (GVHD) remains the major problem to be overcome in allogeneic bone marrow transplantation [1–3]. Despite posttransplant immunosuppressive therapy with cyclosporine or methotrexate, moderate to severe acute GVHD develops in approximately 45% of transplant recipients with an HLA-identical sibling donor [4] and in >75% of patients from HLA-nonidentical relatives [5]. Recently, bone marrow transplants have been performed from unrelated HLA-identical or partially matched related donors [6–10]. Preliminary results indicate that even with phenotypically identical unrelated donor-recipient pairs and the use of combination posttransplant immunosuppressive therapy, the incidence of acute GVHD exceeds 75%.

Keywords

Toxicity Lymphoma Leukemia Anemia Methotrexate 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    van Bekkum DW. Immunologic basis of graft-versus-host disease. In: The Biology of Bone Marrow Transplantation, Gale, Fox, eds. Academic Press, New York, 1988:175–194.Google Scholar
  2. 2.
    Grebe SC, Streilein JW. Graft-versus-host disease. Adv Immunol 1976; 22:119–221.PubMedCrossRefGoogle Scholar
  3. 3.
    Glucksberg H, Storb R, Fefer A. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-identical sibling donors. Transplantation 1974; 18:295–304.PubMedCrossRefGoogle Scholar
  4. 4.
    Champlin RE, Gale RP. Early complications of bone marrow transplantation. Semin Hematol 1984; 21:101–108.PubMedGoogle Scholar
  5. 5.
    Beatty PG, Clift RA, Mickelson EM, et al. Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med 1986; 314:1006–1010.CrossRefGoogle Scholar
  6. 6.
    Hows JM, Yin J, Marsh J, et al. Histocompatible unrelated volunteer donors compared with HLA-nonidentical family donors in marrow transplantation for aplastic anemia and leukemia. Blood 1986; 68:1322–1328.PubMedGoogle Scholar
  7. 7.
    Gingrich RD, Ginder GD, Goeken NE, et al. Allogeneic marrow grafting with mismatched unrelated marrow donors in clinical bone marrow transplantation. Blood 1988; 5:1375–1381.Google Scholar
  8. 8.
    Ash RC, Serwint MS, Coffey C, et al. Allogeneic marrow transplantation for leukemic patients who lack matched sibling donors. Blood 1985; 66 (Suppl 1):264a.Google Scholar
  9. 9.
    Beatty PG, Ash R, Hows JM, McGlave PB. The use of unrelated bone marrow donors in the treatment of patients with chronic myelogenous leukemia: Experience of four marrow transplant centers. Transplantation 1989, in press.Google Scholar
  10. 10.
    O’Reilly PJ. Clinical results of HLA-mismatched bone marrow transplantation. In: Detection and Treatment of Minimal Residual Disease in Acute Leukemia, Lowenberg B, Hagenbeck TS, eds. Martinus Nijhoff, Dordrecht, 1985:35–43.Google Scholar
  11. 11.
    Korngold R, Sprent J. Lethal graft-versus-host disease after bone marrow transplantation across minor histocompatibility barriers in mice. Prevention by removing mature T cells from marrow. J Exp Med 1978; 148:1687–1698.PubMedCrossRefGoogle Scholar
  12. 12.
    Korngold R, Sprent J. Lethal GVHD across minor histocompatibility barriers: Nature of the effector cells and role of the H-2 complex. Immunol Rev 1983; 71:5–29.PubMedCrossRefGoogle Scholar
  13. 13.
    Hamilton BC, Bevan MJ, Parkman R. Antirecipient cytotoxic T-lymphocyte precursors are present in the spleens of mice with acute graft-versus-host disease due to minor histocompatibility antigens. J Immunol 1981; 126:621.PubMedGoogle Scholar
  14. 14.
    Ferrara J, Lipton J, Hellman S, et al. Engraftment following T-cell depleted marrow transplantation I. The role of major and minor histocompatibility barriers. Transplantation 1987; 43:461–467.PubMedCrossRefGoogle Scholar
  15. 15.
    Sakamoto K, Sachs DH, Shimada S, et al. Bone marrow transplantation in miniature swine III. Graft-versus-host disease and the effect of T cell depletion of marrow. Transplantation 1988; 45:869–875.PubMedCrossRefGoogle Scholar
  16. 16.
    Soderling CCB, Chang WS, Blazar BR, et al. A correlation between conditioning and engraftment in recipients of MHC-mismatched T cell-depleted murine bone marrow trans-plants. J Immunol 1985; 135:941–946.PubMedGoogle Scholar
  17. 17.
    Marmont A, et al. for the International Bone Marrow Transplant Registry, in press.Google Scholar
  18. 18.
    Butturini A, Gale RP. T cell depletion in bone marrow transplantation for leukemia: Current results and future directions. Bone Marrow Transplant 1988; 3:185–192.PubMedGoogle Scholar
  19. 19.
    Champlin RE. Bone marrow transplantation for leukemia: Effects of T-cell depletion of donor marrow. Transplant Proc 1986; 21:157–159.Google Scholar
  20. 20.
    Waldmann H, Hale G, Cividalli G, et al. Elimination of graft versus host disease by in vitro depletion of alloreactive lymphocytes with monoclonal rat anti-human lymphocyte antibody (CAMPATH-1). Lancet 1984; 2:483–486.PubMedCrossRefGoogle Scholar
  21. 21.
    Filipovich AH, McGlave PB, Ramsay NKC, et al. Pretreatment of donor bone marrow with monoclonal antibody OKT3 for prevention of acute graft-versus-host disease in allogeneic histocompatible bone marrow transplantation. Lancet 1982; i:1266–1270.CrossRefGoogle Scholar
  22. 22.
    Prentice H, Janossy G, Trejdosiewicz L, et al. Depletion of T lymphocytes in donor marrow prevents significant graft-versus-host disease in matched allogeneic leukemic marrow transplant recipients. Lancet 1984; 1:472–476.PubMedCrossRefGoogle Scholar
  23. 23.
    Mitsuyasu R, Champlin RE, Gale RP, et al. Depletion of T lymphocytes from donor bone marrow for the prevention of graft-versus-host disease following bone marrow transplantation. Ann Intern Med 1986; 105:20–26.PubMedGoogle Scholar
  24. 24.
    Prentice HG, Brenner MK, Janossy G, et al. T-cell depletion using MBG6 and RFT8 monoclonal antibody combination and complement lysis prevents significant acute and chronic GVHD in HLA matched allogeneic marrow transplants. Exp Hematol 1985; 13 (Suppl 17):115–116.Google Scholar
  25. 25.
    Martin PJ, Hansen JA, Buckner CD, et al. Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts. Blood 1985; 66:664–672.PubMedGoogle Scholar
  26. 26.
    Bozdech MJ, Sondei PM, Trigg ME, et al. Transplantation of HLA haploidentical T cell depleted marrow for leukemia: Addition of cytosine arabinoside to the transplant conditioning prevents graft rejection. Exp Hematol 1985; 13:1201–1210.PubMedGoogle Scholar
  27. 27.
    Ritz J, Takvorian T, Anderson K, et al. Prevention of GVHD following allogeneic marrow transplantation by in vitro depletion of mature T lymphocytes from donor marrow using anti-T12 monoclonal antibody and rabbit complement. Blood 1984; 64(Suppl l):219a.Google Scholar
  28. 28.
    Filipovich AH, Vallera DA, Youle RJ, et al. Graft-versus-host disease prevention in allogeneic bone marrow transplantation from histocompatible siblings. Transplantation 1987; 44:62–69.PubMedCrossRefGoogle Scholar
  29. 29.
    Maraninchi D, Gluckman E, Blaise D, et al. Impact of T-cell depletion on outcome of allogeneic bone marrow transplantation for standard-risk leukemias. Lancet 1987; 2: 175–178.PubMedCrossRefGoogle Scholar
  30. 30.
    Filipovich A II, Vallera DA, Youle RJ, et al. Ex-vivo treatment of donor bone marrow with anti-T-cell immunotoxins for prevention of graft vs. host disease. Lancet 1984; 1:469–472.PubMedCrossRefGoogle Scholar
  31. 31.
    Treleaven JG, Gibson FM, Ugelstad J, et al. Removal of neuroblastoma cells from bone marrow with monoclonal antibodies conjugated to magnetic microspheres. Lancet 1984; 1:70–83.PubMedCrossRefGoogle Scholar
  32. 32.
    Reisner Y, O’Reilly RJ, Kapoor N, et al. Allogeneic bone marrow transplantation using stem cells fractioned by lectins: In vitro analysis of soybean agglutinin. Lancet 1980; 2: 1320–1324.PubMedCrossRefGoogle Scholar
  33. 33.
    Wagner JE, Donnenberg AD, Noga SJ, et al. Lymphocyte depletion of donor bone marrow by counterflow centrifugal elutriation: Results of a phase I clinical trial. Blood 1988; 72: 1168–1172.PubMedGoogle Scholar
  34. 34.
    Martin PJ, Hansen JA. Quantitative assays for detection of residual T cells of T-depleted human marrow. Blood 1985; 65:1134–1140.PubMedGoogle Scholar
  35. 35.
    Kernan NA, Collins NA, Juliano L, et al. Clonal T lymphocytes in T-cell depleted bone marrow transplants correlate with the development of GVHD. Blood 1986; 68:770.PubMedGoogle Scholar
  36. 36.
    Reisner Y, Kapoor N, Kirkpatrick D, et al. Transplantation for severe combined immunodeficiency with HLA-A, B, D, Dr incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells. Blood 1983; 61:341–348.PubMedGoogle Scholar
  37. 37.
    Hale G, Waldmann H. Depletion of T-cells with Campath-1 and human complement. Analysis of GVHD and graft-failure in a multicenter study. Bone Marrow Transplant 1986; 1: 93–94.Google Scholar
  38. 38.
    Patterson J, Prentice HG, Brenner MK, et al. Graft rejection following HLA-matched T lymphocyte depleted bone marrow transplantation. Br J Haematol 1986; 63:221–230.PubMedCrossRefGoogle Scholar
  39. 39.
    Kernan NA, Flomenberg N, Dupont B, et al. Graft rejection in recipients of T-cell-depleted HLA-nonidentical marrow transplants for leukemia. Transplantation 1987; 43:842–847.PubMedGoogle Scholar
  40. 40.
    O’Reilly RJ, Collins NH, Kernan N, et al. Transplantation of marrow-depleted T cells by soybean lectin agglutination and E-rosette depletion: Major histocompatibility complex-related graft resistance in leukemic transplant recipients. Transplant Proc 1985; 17:455–459.Google Scholar
  41. 41.
    Martin PJ, Hansen JA, Buckner CD. Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts. Blood 1985; 66:664–672.PubMedGoogle Scholar
  42. 42.
    Reisner Y, Ben-Bassat I, Douer D, et al. Demonstration of clonable alloreactive T ceils in a primate model for bone marrow transplantation. Proc Natl Acad Sci USA 1986; 83: 4012–4015.PubMedCrossRefGoogle Scholar
  43. 43.
    Butturini A, Seeger RC, Gale RP. Recipient immune-competent T lymphocytes can survive intensive conditioning for bone marrow transplantation. Blood 1986; 68:954–956.PubMedGoogle Scholar
  44. 44.
    Schouten HC, Sizoo W, van’t Veer MB, Hagenbeck A, Lowenberg B. Incomplete chi-merism in erythroid myeloid and B-lymphocyte lineage after T-cell depleted allogeneic bone marrow transplantation. Bone Marrow Transplant 1988; 3:407–412.PubMedGoogle Scholar
  45. 45.
    Schwartz E, Lapidot T, Gozes D, et al. Abrogation of bone marrow allograft resistance in mice by increased total body irradiation correlates with eradication of host clonable T cells and alloreactive cytotoxic precursors. J Immunol 1987; 138:460–465.PubMedGoogle Scholar
  46. 46.
    Lapidot T, Singer TS, Salomon O, et al. Booster irradiation to the spleen following total body irradiation: A new immunosuppressive approach for allogeneic bone marrow transplantation. J Immunol 1988; 141:2619–2624.PubMedGoogle Scholar
  47. 47.
    Niederwieser D, Pepe M, Storb R, et al. Improvement in rejection, engraftment rate and survival without increase in graft-versus-host disease by high marrow cell dose in patients transplanted for aplastic anemia. Br J Haematol 1988; 69:23–28.PubMedCrossRefGoogle Scholar
  48. 48.
    Frassoni F, Sessargeo M, Bacigalupo A, et al. Competition between recipient and donor cells after bone marrow transplantation for chronic myelogenous leukemia. Br J Haematol 1988; 69:471–475.PubMedCrossRefGoogle Scholar
  49. 49.
    Anasetti C, Amos D, Beatty PG, et al. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med 1989; 320:197–204.PubMedCrossRefGoogle Scholar
  50. 50.
    Friedrich W, Goldmann SF, Vetter U, et al. Immunoreconstitution in severe combined immunodeficiency after transplantation of HLA-haploidentical T-cell depleted bone marrow. Lancet 1984; 1:761–764.PubMedCrossRefGoogle Scholar
  51. 51.
    Brenner MK, Wimperis JZ, Reittie JE, et al. Recovery of immunoglobulin isotypes following T-cell depleted allogeneic bone marrow transplantation. Br J Haematol 1986; 64:125–132.PubMedCrossRefGoogle Scholar
  52. 52.
    Rooney CM, Wimperis JZ, Brenner MK, et al. Natural killer cell activity following T-cell depleted allogeneic bone marrow transplantation. Br J Haematol 1986; 62:413–420.PubMedCrossRefGoogle Scholar
  53. 53.
    Horowitz MM. Graft-versus-leukemia. In: Bone Marrow Transplantation: Current Controversies, Gale RP, Champlin RE. Alan R Liss, New York, 1988.Google Scholar
  54. 54.
    Butturini A, Bortin MM, Gale RP. Graft-versus-leukemia following bone marrow transplantation. Bone Marrow Transplant 1987; 2:233–242.PubMedGoogle Scholar
  55. 55.
    Gale RP, Champlin RE. How does bone marrow transplantation cure leukemia? Lancet 1984; 2:28–30.PubMedCrossRefGoogle Scholar
  56. 56.
    Okunewick JP, Meredith RF. Graft-Versus-Leukemia in Man and Animal Models. CRC Press, Boca Raton, FL, 1981.Google Scholar
  57. 57.
    Weiden PL, Sullivan KM, Flournoy N, et al. Antileukemic effect of chronic graft-versus-host disease: Contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 1981; 304:1529–1533.PubMedCrossRefGoogle Scholar
  58. 58.
    Bortin MM, Truitt RL, Rimm AA, et al. Graft versus leukemia reactivity induced by allo-immunization without augmentation of graft versus host reactivity. Nature 1979; 281:490–491.PubMedCrossRefGoogle Scholar
  59. 59.
    Storb R, Deeg HJ, Whitehead J, et al. Methotrexate and cyclosporine compared with cyclo-sporine alone for prophylaxis of acute graft-versus-host disease after marrow transplantation for leukemia. N Engl J Med 1986; 314:729–735.PubMedCrossRefGoogle Scholar
  60. 60.
    Storb R, Deeg HJ, Pepe M, et al. Methotrexate and cyclosporine versus cyclosporine alone for prophylaxis of graft-versus-host disease in patients given HLA-identical marrow grafts for leukemia: Long-term follow-up of a controlled trial. Blood 1989; 73:1729–1734.PubMedGoogle Scholar
  61. 61.
    Goldman JM, Gale RP, Bortin MM, et al. Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: Increased risk of relapse associated with T-cell depletion. Ann Intern Med 1988; 108:806–814.PubMedGoogle Scholar
  62. 62.
    Trigg ME, Billing R, Sondei PM, et al. Clinical trials depleting T lymphocytes from donor bone marrow for matched and mismatched allogeneic bone marrow transplants. Cancer Treat Rep 1985; 69:377.PubMedGoogle Scholar
  63. 63.
    Shapiro RS, McClain K, Frizzera G, et al. Epstein-Barr virus associated B-cell lympho-proliferative disorders following bone marrow transplantation. Blood 1988; 71:1234–1243.PubMedGoogle Scholar
  64. 64.
    Zutter MM, Martin PJ, Sale GE, et al. Epstein-Barr virus lymphoproliferation after bone marrow transplantation. Blood 1988; 72:520–529.PubMedGoogle Scholar
  65. 65.
    Champlin RE, Horowitz MM, van Bekkum DW, et al. Graft failure following bone marrow transplantation for severe aplastic anemia: Risk factors and treatment results. Blood 1989; 73:606–613.PubMedGoogle Scholar
  66. 66.
    Reisner Y, Lapidot T, Schwartz E, et al. Rejection of T cell depleted bone marrow allograft in mice and primates. In: T Cell Depletion in Allogeneic Bone Marrow Transplantation. Martelli MF, Grignani F, Reisnery, eds. Ares-Serono Symposia, Rome, 1988:37.Google Scholar
  67. 67.
    Champlin RE, Ho W, Mitsuyasu R, et al. Graft failure and leukemia relapse following T lymphocyte depleted bone marrow transplants; effect of intensification of immunosuppressive conditioning. Transplant Proc 1987; 19:2616–2619.PubMedGoogle Scholar
  68. 68.
    Slavin S. Total lymphoid irradiation (TO). Immunol Today 1987; 8:88–92.CrossRefGoogle Scholar
  69. 69.
    Henslee PJ, Thompson JS, Romond EH, et al. T-cell depletion of HLA-and haploidentical marrow reduces graft-versus-host disease but it may impair a graft-versus-leukemia effect. Transplant Proc 1987; 19:2701–2706.PubMedGoogle Scholar
  70. 70.
    Fischer A, Blanche S, Veber F, et al. Prevention of graft failure by an anti-HLFA-I monoclonal antibody in HLA-mismatched bone marrow transplantation. Lancet 1986; 1:1058–1061.CrossRefGoogle Scholar
  71. 71.
    Gratwohl A, Tichelli A, Wursch A, et al. Irradiated donor buffy coat following T-cell-depleted bone marrow transplants. Bone Marrow Transplantation 1988; 3:577–582.PubMedGoogle Scholar
  72. 72.
    Smith BR, Rappeport JM, Lipton JM, et al. Marrow T cell depletion with anti Leul monoclonal antibody (Mab) and complement in matched and mismatched bone marrow transplantation (BMT). Blood 1984; 64(Suppl l):221a.Google Scholar
  73. 73.
    Korngold R, Sprent J. Variable capacity of L3T4+ T cells to cause lethal graft-versus-host disease across minor histocompatibility barriers in mice. J Exp Med 1987; 165:52–64.CrossRefGoogle Scholar
  74. 74.
    Maraninchi D, Mawas C, Guyotat D, et al. Selective depletion of marrow-T cytotoxic lymphocytes (CDS) in the prevention of graft-versus-host disease after allogeneic bone-marrow transplantation. Transplant Int 1988; 1:91–94.Google Scholar
  75. 75.
    Champlin RE, Gajewski J, Feig SA, et al. Selective depletion of CD8 positive T lymphocytes for prevention of graft-versus-host disease following bone marrow transplantation. Transplant Proc 1989; 21:2947–2948.PubMedGoogle Scholar
  76. 76.
    Brandt SJ, Peters WP, Antwater SK, et al. Effect of recombinant human granulocyte, macrophage-colony stimulating factor on hematopoietic reconstitution after high dose chemotherapy and autologous bone marrow transplantation. N Engl J Med 1988; 318: 869–876.PubMedCrossRefGoogle Scholar
  77. 77.
    Neumanitis J, Singer JW, Buckner CD, et al. Use of recombinant human granulocyte-macrophage colony-stimulating factor in autologous marrow transplantation for lymphoid malignancies. Blood 1988; 72:834–836.Google Scholar
  78. 78.
    Blazar BR, Widme MB, Soderling CCB, et al. Augmentation of donor bone marrow engraftment in histoincompatible murine recipients by granulocyte/macrophage colony-stimulating factor. Blood 1988; 71:320.PubMedGoogle Scholar
  79. 79.
    Blazar BR, Widmen MB, Soderling CCB, Gillis S, Vallera D. Enhanced survival but reduced engraftment in murine recipients of recombinant granulocyte/macrophage colony-stimulating factor following transplantation of T-cell depleted histoincompatible bone marrow. Blood 1988; 72:1148–1154.PubMedGoogle Scholar
  80. 80.
    Vallera DA, Blazar BR. Depressed leukocyte reconstitution and engraftment in murine recipients of T cell depleted histoincompatible marrow pretreated with interleukin 3. Transplantation 1988; 46(4):616–620.PubMedCrossRefGoogle Scholar
  81. 81.
    Sykes M, Sheard M, Sachs DH. Effects of T cell depletion in radiation bone marrow chimeras. Evidence for a donor cell population which increases allogeneic chimerism but which lacks the potential to produce GVHD. J Immunol 1988; 141:2282–2288.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1990

Authors and Affiliations

  • Richard E. Champlin

There are no affiliations available

Personalised recommendations