Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Meeting Report
  • Published:

Should we T cell deplete sibling grafts for acute myeloid leukaemia in first remission?

An Erratum to this article was published on 09 February 2004

Summary:

There is controversy regarding the best approach to the management of patients with acute myeloid leukaemia (AML) in first remission (CR1). The impact of matched related allogeneic transplant in CR1 on the overall survival is equivocal, but what is not in doubt is a significant reduction in the relapse risk, compared to both autologous transplants and intensive chemotherapy, which is because of the allogeneic or the graft-versus-leukaemia (GVL) effect. Yet, this does not always translate to improved survival. T cell depletion (TCD) can reduce deaths related to graft-versus-host disease (GVHD) and its therapy, but might increase the relapse risk. The existing literature suggests that TCD is associated with a disease-free survival (DFS) of 53–80% and is associated with a lower relapse risk than anticipated (0–30%). We discuss the evolution of TCD in allogeneic transplantation and its relevance in AML-CR1 with regard to GVHD, DFS, immune reconstitution and GVL effect. It is possible that by reducing TRM related to GVHD and extramedullary toxicities, particularly in the older patients, TCD might improve the impact of allogeneic transplantation in AML-CR1, provided the immune reconstitution and the relapse risk are not adversely affected. Randomised studies are underway to address these issues.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Zittoun RA, Mandelli F, Willemze R et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. N Engl J Med 1995; 332: 217–223.

    Article  CAS  PubMed  Google Scholar 

  2. Woods WG, Neudorf S, Gold S et al. A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission. Blood 2001; 97: 56–62.

    Article  CAS  PubMed  Google Scholar 

  3. Tallman MS, Rowlings PA, Milone G et al. Effect of postremission chemotherapy before human leukocyte antigen-identical sibling transplantation for acute myelogenous leukemia in first complete remission. Blood 2000; 96: 1254–1258.

    CAS  PubMed  Google Scholar 

  4. Slovak ML, Kopecky KJ, Cassileth PA et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 2000; 96: 4075–4083.

    Article  CAS  PubMed  Google Scholar 

  5. Cassileth PA, Harrington DP, Appelbaum FR et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med 1998; 339: 1649–1656.

    Article  CAS  PubMed  Google Scholar 

  6. Burnett AK, Wheatley K, The Medical Research Council Adult and Paediatric Working Parties et al. The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial. Br J Haematol 2002; 118: 385–400.

    Article  PubMed  Google Scholar 

  7. Frassoni F . Randomised studies in acute myeloid leukaemia: the double truth. Bone Marrow Transplant 2000; 25: 471–473.

    Article  CAS  PubMed  Google Scholar 

  8. Ho VT, Soiffer RJ . The history and future of T cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation. Blood 2001; 98: 3192–3204.

    Article  CAS  PubMed  Google Scholar 

  9. Via CS, Finkelman FD . Critical role of interleukin-2 in the development of acute graft-versus-host disease. Int Immunol 1993; 5: 565–572.

    Article  CAS  PubMed  Google Scholar 

  10. Ferrera JLM, Antin JH . Pathophysiology of graft-versus-host disease. In: Thomas ED, Blume KG, Forman SJ (eds) Haematopoetic Stem Cell Transplantation. Blackwell Scientific Publications: Boston, MA, 1999, pp 305–315.

    Google Scholar 

  11. Nozawa K, Ohata J, Sakurai J et al. Preferential blockade of CD8(+) T cell responses by administration of anti-CD137 ligand monoclonal antibody results in differential effect on development of murine acute and chronic graft-versus-host diseases. J Immunol 2001; 167: 4981–4986.

    Article  CAS  PubMed  Google Scholar 

  12. Hollander GA, Widmer B, Burakoff SJ . Loss of normal thymic repertoire selection and persistence of autoreactive T cells in graft vs host disease. J Immunol 1994; 152: 1609–1617.

    CAS  PubMed  Google Scholar 

  13. Hess A, Thoburn C, Chen W et al. Autoreactive T cell subsets in acute and chronic syngeneic graft-versus-host disease. Transplant Proc 2001; 33: 1754–1756.

    Article  CAS  PubMed  Google Scholar 

  14. Nash RA, Pepe MS, Storb R et al. Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate. Blood 1992; 80: 1838–1845.

    Article  CAS  PubMed  Google Scholar 

  15. Ratanatharathorn V, Nash RA, Przepiorka D et al. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood 1998; 92: 2303–2314.

    CAS  PubMed  Google Scholar 

  16. Sullivan KM, Shulman HM, Storb R et al. Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood 1981; 57: 267–276.

    Article  CAS  PubMed  Google Scholar 

  17. Schmitz N, Beksac M, Hasenclever D et al. Transplantation of mobilized peripheral blood cells to HLA-identical siblings with standard-risk leukemia. Blood 2002; 100: 761–767.

    Article  CAS  PubMed  Google Scholar 

  18. Cutler C, Giri S, Jeyapalan S et al. Acute and chronic graft-versus-host disease after allogeneic peripheral-blood stem-cell and bone marrow transplantation: a meta-analysis. J Clin Oncol 2001; 19: 3685–3691.

    Article  CAS  PubMed  Google Scholar 

  19. Prentice HG, Blacklock HA, Janossy G et al. Depletion of T lymphocytes in donor marrow prevents significant graft-versus-host disease in matched allogeneic leukaemic marrow transplant recipients. Lancet 1984; 1: 472–476.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  CAS  PubMed  Google Scholar 

  21. Herve P, Flesch M, Cahn JY et al. Removal of marrow T cells with OKT3-OKT11 monoclonal antibodies and complement to prevent acute graft-versus-host disease. A pilot study in ten patients. Transplantation 1985; 39: 138–143.

    Article  CAS  PubMed  Google Scholar 

  22. Soiffer RJ, Murray C, Mauch P et al. Prevention of graft-versus-host disease by selective depletion of CD6-positive T lymphocytes from donor bone marrow. J Clin Oncol 1992; 10: 1191–1200.

    Article  CAS  PubMed  Google Scholar 

  23. Kernan NA, Flomenberg N, Collins NH et al. Quantitation of T lymphocytes in human bone marrow by a limiting dilution assay. Transplantation 1985; 40: 317–322.

    Article  CAS  PubMed  Google Scholar 

  24. Korngold B, 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.

    Article  CAS  PubMed  Google Scholar 

  25. Korbling M, Anderlini P . Peripheral blood stem cell versus bone marrow allotransplantation: does the source of hematopoietic stem cells matter? Blood 2001; 98: 2900–2908.

    Article  CAS  PubMed  Google Scholar 

  26. Wagner JE, Santos GW, Noga SJ et al. Bone marrow graft engineering by counterflow centrifugal elutriation: results of a phase I–II clinical trial. Blood 1990; 75: 1370–1377.

    Article  CAS  PubMed  Google Scholar 

  27. Kernan NA, Collins NH, Juliano L et al. Clonable T lymphocytes in T cell-depleted bone marrow transplants correlate with development of graft-v-host disease. Blood 1986; 68: 770–773.

    Article  CAS  PubMed  Google Scholar 

  28. Urbano-Ispizua A, Rozman C, Pimentel P et al. Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings. Blood 2002; 100: 724–727.

    Article  CAS  PubMed  Google Scholar 

  29. Urbano-Ispizua A, Rozman C, Pimentel P et al. The number of donor CD3(+) cells is the most important factor for graft failure after allogeneic transplantation of CD34(+) selected cells from peripheral blood from HLA-identical siblings. Blood 2001; 97: 383–387.

    Article  CAS  PubMed  Google Scholar 

  30. Aversa F, Tabilio A, Velardi A et al. Treatment of high-risk acute leukemia with T cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 1998; 339: 1186–1193.

    Article  CAS  PubMed  Google Scholar 

  31. 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.

    Article  CAS  PubMed  Google Scholar 

  32. Martin PJ, Hansen JA, Torok-Storb B et al. Graft failure in patients receiving T cell-depleted HLA-identical allogeneic marrow transplants. Bone Marrow Transplant 1988; 3: 445–456.

    CAS  PubMed  Google Scholar 

  33. Kernan NA, Bordignon C, Heller G et al. Graft failure after T cell-depleted human leukocyte antigen identical marrow transplants for leukemia: I. Analysis of risk factors and results of secondary transplants. Blood 1989; 74: 2227–2236.

    Article  CAS  PubMed  Google Scholar 

  34. Papadopoulos EB, Carabasi MH, Castro-Malaspina H et al. T cell-depleted allogeneic bone marrow transplantation as postremission therapy for acute myelogenous leukemia: freedom from relapse in the absence of graft-versus-host disease. Blood 1998; 91: 1083–1090.

    Article  CAS  PubMed  Google Scholar 

  35. Hale G, Zhang MJ, Bunjes D et al. Improving the outcome of bone marrow transplantation by using CD52 monoclonal antibodies to prevent graft-versus-host disease and graft rejection. Blood 1998; 92: 4581–4590.

    Article  CAS  PubMed  Google Scholar 

  36. Potter MN, Pamphilon DH, Cornish JM et al. Graft-versus-host disease in children receiving HLA-identical allogeneic bone marrow transplants with a low adjusted T lymphocyte dose. Bone Marrow Transplant 1991; 8: 357–361.

    CAS  PubMed  Google Scholar 

  37. Bachar-Lustig E, Rachamim N, Li HW et al. Megadose of T cell-depleted bone marrow overcomes MHC barriers in sublethally irradiated mice. Nat Med 1995; 1: 1268–1273.

    Article  CAS  PubMed  Google Scholar 

  38. Steffens HP, Podlech J, Kurz S et al. Cytomegalovirus inhibits the engraftment of donor bone marrow cells by downregulation of hemopoietin gene expression in recipient stroma. J Virol 1998; 72: 5006–5015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Johnston RE, Geretti AM, Prentice HG et al. HHV-6-related secondary graft failure following allogeneic bone marrow transplantation. Br J Haematol 1999; 105: 1041–1043.

    Article  CAS  PubMed  Google Scholar 

  40. Witherspoon RP, Lum LG, Storb R . Immunologic reconstitution after human marrow grafting. Semin Hematol 1984; 21: 2–10.

    CAS  PubMed  Google Scholar 

  41. Mackall CL, Granger L, Sheard MA et al. T cell regeneration after bone marrow transplantation: differential CD45 isoform expression on thymic-derived versus thymic-independent progeny. Blood 1993; 82: 2585–2594.

    Article  CAS  PubMed  Google Scholar 

  42. Roux E, Helg C, Dumont-Girard F et al. Analysis of T cell repopulation after allogeneic bone marrow transplantation: significant differences between recipients of T cell depleted and unmanipulated grafts. Blood 1996; 87: 3984–3992.

    Article  CAS  PubMed  Google Scholar 

  43. Lowdell MW, Craston R, Ray N et al. The effect of T cell depletion with Campath-1M on immune reconstitution after chemotherapy and allogeneic bone marrow transplant as treatment for leukaemia. Bone Marrow Transplant 1998; 21: 679–686.

    Article  CAS  PubMed  Google Scholar 

  44. Davison GM, Novitzky N, Kline A et al. Immune reconstitution after allogeneic bone marrow transplantation depleted of T cells. Transplantation 2000; 69: 1341–1347.

    Article  CAS  PubMed  Google Scholar 

  45. Small TN, Papadopoulos EB, Boulad F et al. Comparison of immune reconstitution after unrelated and related T cell-depleted bone marrow transplantation: effect of patient age and donor leukocyte infusions. Blood 1999; 93: 467–480.

    Article  CAS  PubMed  Google Scholar 

  46. Chakrabarti S, Mackinnon S, Chopra R et al. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution. Blood 2002; 99: 4357–4363.

    Article  CAS  PubMed  Google Scholar 

  47. Chakrabarti S, Mautner V, Osman H et al. Adenovirus infections following allogeneic stem cell transplantation: the incidence and outcome in relation to graft manipulation, immunosuppression and immune recovery. Blood 2002; 100: 1619–1627.

    Article  CAS  PubMed  Google Scholar 

  48. Martinez C, Urbano-Ispizua A, Rozman C et al. Immune reconstitution following allogeneic peripheral blood progenitor cell transplantation: comparison of recipients of positive CD34+ selected grafts with recipients of unmanipulated grafts. Exp Hematol 1999; 27: 561–568.

    Article  CAS  PubMed  Google Scholar 

  49. Soiffer RJ, Dear K, Rabinowe SN et al. Hepatic dysfunction following T cell-depleted allogeneic bone marrow transplantation. Transplantation 1991; 52: 1014–1019.

    Article  CAS  PubMed  Google Scholar 

  50. Ho VT, Weller E, Lee SJ et al. Prognostic factors for early severe pulmonary complications after hematopoetic stem cell transplantation. Biol Blood Marrow Transplant 2001; 7: 223–229.

    Article  CAS  PubMed  Google Scholar 

  51. Shulman HM, Hinterberger W . Hepatic veno-occlusive disease – liver toxicity syndrome after bone marrow transplantation. Bone Marrow Transplant 1992; 10: 197–214.

    CAS  PubMed  Google Scholar 

  52. Foley R, Couban S, Walker I et al. Monitoring soluble interleukin-2 receptor levels in related and unrelated donor allogenic bone marrow transplantation. Bone Marrow Transplant 1998; 21: 769–773.

    Article  CAS  PubMed  Google Scholar 

  53. Cooke KR, Krenger W, Hill G et al. Host reactive donor T cells are associated with lung injury after experimental allogeneic bone marrow transplantation. Blood 1998; 92: 2571–2580.

    Article  CAS  PubMed  Google Scholar 

  54. Cooke KR, Kobzik L, Martin TR et al. An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation: I. The roles of minor H antigens and endotoxin. Blood 1996; 88: 3230–3239.

    Article  CAS  PubMed  Google Scholar 

  55. Keever-Taylor CA, Craig A, Molter M et al. Complement-mediated T cell depletion of bone marrow: comparison of T10B9.1A-31 and Muromonab-Orthoclone OKT3. Cytotherapy 2001; 3: 467–481.

    Article  CAS  PubMed  Google Scholar 

  56. Waldmann H . A personal history of the CAMPATH-1H antibody. Med Oncol 2002; 19 (Suppl): S3–S9.

    Article  PubMed  Google Scholar 

  57. Hale G . The CD52 antigen and development of the CAMPATH antibodies. Cytotherapy 2001; 3: 137–143.

    Article  CAS  PubMed  Google Scholar 

  58. Klangsinsirikul P, Carter GI, Byrne JL et al. Campath-1G causes rapid depletion of circulating host dendritic cells (DCs) before allogeneic transplantation but does not delay donor DC reconstitution. Blood 2002; 99: 2586–2591.

    Article  CAS  PubMed  Google Scholar 

  59. Champlin RE, Passweg JR, Zhang M et al. T cell depletion of bone marrow transplants for leukaemia from donors other than HLA-identical siblings: advantage of T cell antibodies with narrow specificities. Blood 2000; 95: 3996–4003.

    CAS  PubMed  Google Scholar 

  60. Hale G, Waldmann H . Risks of developing Epstein–Barr virus-related lymphoproliferative disorders after T cell-depleted marrow transplants. CAMPATH users. Blood 1998; 91: 3079.

    Article  CAS  PubMed  Google Scholar 

  61. Rebello P, Cwynarsky K, Varughese M et al. Pharmaco-kinetics of Campath-1H in bone marrow transplant patients. Cytotherapy 2002; 3: 261–267.

    Article  Google Scholar 

  62. Marmont AM, Horowitz MM, Gale RP et al. T cell depletion of HLA-identical transplants in leukemia. Blood 1991; 78: 2120–2130.

    Article  CAS  PubMed  Google Scholar 

  63. Aversa F, Terenzi A, Carotti A et al. Improved outcome with T cell-depleted bone marrow transplantation for acute leukemia. J Clin Oncol 1999; 17: 1545–1550.

    Article  CAS  PubMed  Google Scholar 

  64. Soiffer RJ, Fairclough D, Robertson M et al. CD6-depleted allogeneic bone marrow transplantation for acute leukemia in first complete remission. Blood 1997; 89: 3039–3047.

    Article  CAS  PubMed  Google Scholar 

  65. Schattenberg A, Schaap N, Preijers F et al. Outcome of T cell-depleted transplantation after conditioning with an intensified regimen in patients aged 50 years or more is comparable with that in younger patients. Bone Marrow Transplant 2000; 26: 17–22.

    Article  CAS  PubMed  Google Scholar 

  66. Kroger N, Zabelina T, Kruger W et al. In vivo T cell depletion with pretransplant anti-thymocyte globulin reduces graft-versus-host disease without increasing relapse in good risk myeloid leukemia patients after stem cell transplantation from matched related donors. Bone Marrow Transplant 2002; 29: 683–689.

    Article  CAS  PubMed  Google Scholar 

  67. Bunjes D, Hertenstein B, Wiesneth M et al. In vivo/ex vivo T cell depletion reduces the morbidity of allogeneic bone marrow transplantation in patients with acute leukaemias in first remission without increasing the risk of treatment failure: comparison with cyclosporin/methotrexate. Bone Marrow Transplant 1995; 15: 563–568.

    CAS  PubMed  Google Scholar 

  68. Novitzky N, Thomas V, Hale G et al. Ex vivo depletion of T cells from bone marrow grafts with CAMPATH-1 in acute leukemia: graft-versus-host disease and graft-versus-leukemia effect. Transplantation 1999; 67: 620–626.

    Article  CAS  PubMed  Google Scholar 

  69. Barge RM, Brouwer RE, Beersma MF et al. Comparison of allogeneic T cell-depleted peripheral blood stem cell and bone marrow transplantation: effect of stem cell source on short- and long-term outcome. Bone Marrow Transplant 2001; 27: 1053–1058.

    Article  CAS  PubMed  Google Scholar 

  70. Hale G, Jacobs P, Wood L et al. CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells. Bone Marrow Transplant 2000; 26: 69–76.

    Article  CAS  PubMed  Google Scholar 

  71. Chakrabarti S, MacDonald D, Hale G et al. T cell depletion with Campath-1H ‘in the bag’ for matched related allogeneic peripheral blood stem cell transplantation is associated with reduced graft-versus-host disease, rapid immune constitution and improved survival. Br J Haematol 2003; 121: 109–118.

    Article  PubMed  Google Scholar 

  72. Sugita K, Soiffer RJ, Murray C et al. The phenotype and reconstitution of immunoregulatory T cell subsets after T cell-depleted allogeneic and autologous bone marrow transplantation. Transplantation 1994; 57: 1465–1473.

    Article  CAS  PubMed  Google Scholar 

  73. Storek J, Dawson MA, Storer B et al. Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation. Blood 2001; 97: 3380–3389.

    Article  CAS  PubMed  Google Scholar 

  74. Martinez C, Urbano-Ispizua A, Rozman C et al. Immune reconstitution following allogeneic peripheral blood progenitor cell transplantation: comparison of recipients of positive CD34+ selected grafts with recipients of unmanipulated grafts. Exp Hematol 1999; 27: 561–568.

    Article  CAS  PubMed  Google Scholar 

  75. Chakraverty R, Robinson S, Peggs K et al. Excessive T cell depletion of peripheral blood stem cells has an adverse effect upon outcome following allogeneic stem cell transplantation. Bone Marrow Transplant 2001; 28: 827–834.

    Article  CAS  PubMed  Google Scholar 

  76. Bacigalupo A, Lamparelli T, Gualandi F et al. Increased risk of leukemia relapse with high dose cyclosporine after allogeneic marrow transplantation for acute leukemia: a 10 year follow-up of a randomized study. Blood 2001; 98: 3174–3175.

    Article  CAS  Google Scholar 

  77. Kumar S, Chen MG, Gastineau DA et al. Effect of slow lymphocyte recovery and type of graft-versus-host disease prophylaxis on relapse after allogeneic bone marrow transplantation for acute myelogenous leukemia. Bone Marrow Transplantation 2001; 28: 951–956.

    Article  CAS  PubMed  Google Scholar 

  78. Powles R, Singhal S, Treleaven J et al. Identification of patients who may benefit from prophylactic immunotherapy after bone marrow transplantation for acute myeloid leukemia on the basis of lymphocyte recovery early after transplantation. Blood 1998; 91: 3481–3486.

    Article  CAS  PubMed  Google Scholar 

  79. 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.

    Article  CAS  PubMed  Google Scholar 

  80. Ruggeri L, Capanni M, Urbani E et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002; 295: 2097–2100.

    Article  CAS  PubMed  Google Scholar 

  81. Orleans-Lindsay JK, Barber LD, Prentice HG et al. Acute myeloid leukaemia cells secrete a soluble factor that inhibits T and NK cell proliferation but not cytolytic function – implications for the adoptive immunotherapy of leukaemia. Clin Exp Immunol 2001; 126: 403–411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Yan Y, Steinherz P, Klingemann HG et al. Antileukemia activity of a natural killer cell line against human leukemias. Clin Cancer Res 1998; 4: 2859–2868.

    CAS  PubMed  Google Scholar 

  83. Lowdell MW, Ray N, Craston R et al. The in vitro detection of anti-leukaemia-specific cytotoxicity after autologous bone marrow transplantation for acute leukaemia. Bone Marrow Transplant 1997; 19: 891–897.

    Article  CAS  PubMed  Google Scholar 

  84. Chakrabarti S . Critical factors in optimizing graft-versus-leukemia effect for relapsed leukemias. J Clin Oncol 2002; 20: 2756.

    Article  PubMed  Google Scholar 

  85. Chen X, Regn S, Raffegerst S et al. Interferon alpha in combination with GM-CSF induces the differentiation of leukaemic antigen-presenting cells that have the capacity to stimulate a specific anti-leukaemic cytotoxic T cell response from patients with chronic myeloid leukaemia. Br J Haematol 2000; 111: 596–607.

    CAS  PubMed  Google Scholar 

  86. Chakrabarti S, Brown J, Guttridge M et al. Early lymphocyte recovery is an important determinant of outcome following allogeneic transplantation with CD34+ selected graft and limited T cell addback. Bone Marrow Transplant 2003; 32: 23–30.

    Article  CAS  PubMed  Google Scholar 

  87. Einsele H, Roosnek E, Rufer N et al. Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood 2002; 99: 3916–3922.

    Article  CAS  PubMed  Google Scholar 

  88. Rooney CM, Smith CA, Ng CYC et al. Infusion of cytotoxic T cells for the prevention and treatment of Epstein–Barr virus-induced lymphoma in allogeneic transplant recipients. Blood 1998; 92: 1549–1555.

    Article  CAS  PubMed  Google Scholar 

  89. Gillespie G, Mutis T, Schrama E et al. HLA class I-minor histocompatibility antigen tetramers select cytotoxic T cells with high avidity to the natural ligand. Hematol J 2000; 1: 403–410.

    Article  CAS  PubMed  Google Scholar 

  90. Ohminami H, Yasukawa M, Fujita S . HLA class I-restricted lysis of leukemia cells by a CD8(+) cytotoxic T-lymphocyte clone specific for WT1 peptide. Blood 2000; 95: 286–293.

    Article  CAS  PubMed  Google Scholar 

  91. Molldrem JJ, Clave E, Jiang YZ et al. Cytotoxic T lymphocytes specific for a nonpolymorphic proteinase 3 peptide preferentially inhibit chronic myeloid leukemia colony-forming units. Blood 1997; 90: 2529–2534.

    Article  CAS  PubMed  Google Scholar 

  92. Hsieh MH, Varadi G, Flomenberg N et al. Leucyl-leucine methyl ester-treated haploidentical donor lymphocyte infusions can mediate graft-versus-leukemia activity with minimal graft-versus-host disease risk. Biol Blood Marrow Transplant 2002; 8: 303–315.

    Article  CAS  PubMed  Google Scholar 

  93. Krijanovski OI, Hill GR, Cooke KR et al. Keratinocyte growth factor separates graft-versus-leukemia effects from graft-versus-host disease. Blood 1999; 94: 825–831.

    Article  CAS  PubMed  Google Scholar 

  94. Panoskaltsis-Mortari A, Taylor PA, Rubin JS et al. Keratinocyte growth factor facilitates alloengraftment and ameliorates graft-versus-host disease in mice by a mechanism independent of repair of conditioning-induced tissue injury. Blood 2000; 96: 4350–4356.

    Article  CAS  PubMed  Google Scholar 

  95. Koc ON, Lazarus HM . Mesenchymal stem cells: heading into the clinic. Bone Marrow Transplant 2001; 27: 235–239.

    Article  CAS  PubMed  Google Scholar 

  96. Bartholomew A, Sturgeon C, Nelson M et al. Allogeneic mesenchymal stem cells have significant immunosuppressive activity. Exp Hematol 1999; 27: 123a.

    Google Scholar 

  97. Tanaka J, Asaka M, Imamura M . T cell co-signalling molecules in graft-versus-host disease. Ann Hematol 2000; 79: 283–290.

    Article  CAS  PubMed  Google Scholar 

  98. Yu XZ, Bidwell SJ, Martin PJ et al. CD28-specific antibody prevents graft-versus-host disease in mice. J Immunol 2000; 164: 4564–4568.

    Article  CAS  PubMed  Google Scholar 

  99. Blazar BR, Taylor PA, Noelle RJ et al. CD4(+) T cells tolerized ex vivo to host alloantigen by anti-CD40 ligand (CD40L:CD154) antibody lose their graft-versus-host disease lethality capacity but retain nominal antigen responses. J Clin Invest 1998; 102: 473–482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Guinan EC, Boussiotis VA, Neuberg D et al. Transplantation of anergic histoincompatible bone marrow allografts. N Engl J Med 1999; 340: 1704–1714.

    Article  CAS  PubMed  Google Scholar 

  101. Gorgun G, Miller KB, Foss FM . Immunologic mechanisms of extracorporeal photochemotherapy in chronic graft-versus-host disease. Blood 2002; 100: 941–947.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to S Chakrabarti or D I Marks.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chakrabarti, S., Marks, D. Should we T cell deplete sibling grafts for acute myeloid leukaemia in first remission?. Bone Marrow Transplant 32, 1039–1050 (2003). https://doi.org/10.1038/sj.bmt.1704281

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704281

Keywords

This article is cited by

Search

Quick links