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T Cell Depletion

The impact of partial T cell depletion on overall transplant-related toxicity, graft function and survival after HLA-identical allogeneic bone marrow transplantation in standard risk adult patients with leukemia

Abstract

In this single-center study, a consecutive cohort of 59 adult patients transplanted with HLA-identical bone marrow and receiving graft-versus-host disease (GVHD) prophylaxis with either standard cyclosporine/methotrexate (n = 33) or partial T cell depletion (E-rosetting) (TCD, n = 26 were analyzed). Only patients with chronic myeloid leukemia in first chronic phase or acute leukemia/myelodysplasia in first or second remission were included. Except for age (median 28 vs 42 years), both groups were comparable in terms of diagnosis, conditioning regimen and growth factor support. TCD significantly reduced >grade II acute GVHD (0 vs 24%, P = 0.02), chronic GVHD (8.5 vs 45%, P = 0.007) and other major bone marrow transplant (BMT)-related complications (4 vs 36%, P = 0.005). TCD decreased overall transplant-related mortality (11.5 vs 36%, P = 0.04). In the TCD group faster neutrophil (13 vs 22 days, P = 0.02) and platelet recoveries (18 vs 26 days, P < 0.001) were noted. The relapse risk was higher after TCD (57.5 vs 21.5%, P = 0.04). Overall survival probability at 10 years was identical in both groups (54 vs 53.5%, P = 0.33). We found a relationship between the number of T cells in the graft and the occurrence of major complications (P < 0.001) and relapse (P = 0.03). This comparative analysis shows that graft-derived T cells have a major role in overall BMT-related toxicity and that partial TCD is an acceptable approach in terms of survival for patients between 40 and 50 years of age. Bone Marrow Transplantation (2001) 28, 917–922.

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References

  1. Gratwohl A, Hermans J, Goldman JM et al. Risk assessment for patients with chronic myeloid leukemia before allogeneic blood or marrow transplantation Lancet 1998 352: 1087–1092

    Article  CAS  PubMed  Google Scholar 

  2. Zikos P, Van Lint MT, Frassoni F et al. Low transplant mortality in allogeneic bone marrow transplantation for acute myeloid leukemia: a randomized study of low-dose cyclosporin versus low-dose cyclosporin and low-dose methotrexate Blood 1998 91: 3503–3508

    CAS  PubMed  Google Scholar 

  3. Weisdorf D, Hakke R, Blazar B et al. Risk factors for acute graft-versus-host disease in histocompatible donor bone marrow transplantation Transplantation 1991 51: 1197–1203

    Article  CAS  PubMed  Google Scholar 

  4. Atkinson K, Horowitz MM, Gale RP et al. Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation Blood 1990 75: 2459–2464

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  6. 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 leukemias 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 

  7. Schmeiser T, Wiesneth M, Bunjes D et al. Infectious complications after allogeneic bone marrow transplantation with and without T-cell depletion of donor marrow Infection 1989 17: 124–130

    Article  CAS  PubMed  Google Scholar 

  8. Delain M, Cahn JY, Racadot E et al. Graft failure after T cell depleted HLA identical allogeneic bone marrow transplantation: risk factors in leukemic patients Leuk Lymphoma 1993 11: 359–368

    Article  CAS  PubMed  Google Scholar 

  9. Naparstek E, Delukina M, Or R et al. Engraftment of marrow allografts treated with Campath-1 monoclonal antibodies Exp Hematol 1999 27: 1210–1218

    Article  CAS  PubMed  Google Scholar 

  10. Lees SJ, Weller E, Alyea EP et al. Efficacy and costs of granulocyte colony-stimulating factor in allogeneic T-cell depleted bone marrow transplantation Blood 1998 92: 2725–2729

    Google Scholar 

  11. Verdonck LF, Dekker AW, de Gast GC et al. Allogeneic bone marrow transplantation with a fixed low number of T-cells in the marrow graft Blood 1994 83: 3090–3096

    CAS  PubMed  Google Scholar 

  12. 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

    CAS  PubMed  Google Scholar 

  13. Novitsky N, Thomas V, Hale G, Waldmann H . 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  Google Scholar 

  14. De Waele M, Renmans W, Segers E et al. An immunogold–silver staining method for detection of cell-surface antigens in cell smears J Histochem Cytochem 1989 37: 935–939

    Article  Google Scholar 

  15. Glucksberg H, Storb R, Fefer A et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors Transplantation 1974 18: 295–304

    Article  CAS  PubMed  Google Scholar 

  16. Shulman HM, Sullivan KM, Weiden PM et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathological study of 20 Seattle patients Am J Med 1980 69: 204–217

    Article  CAS  PubMed  Google Scholar 

  17. Schots R, Kaufman L, Van Riet I et al. Monitoring of C-reactive protein after allogeneic bone marrow transplantation identifies patients at risk of severe transplant-related complications and mortality Bone Marrow Transplant 1998 22: 79–85

    Article  CAS  PubMed  Google Scholar 

  18. McDonald GB, Sharma P, Matthews DE et al. Venocclusive disease of the liver: diagnosis, incidence and predisposing factors Hepatology 1984 4: 116–122

    Article  CAS  PubMed  Google Scholar 

  19. Martin PJ . The role of donor lymphoid cells in allogeneic engraftment Bone Marrow Transplant 1990 6: 283–289

    CAS  PubMed  Google Scholar 

  20. Noga SJ, Seber A, Davis JM et al. CD34 augmentation improves allogeneic T cell-depleted bone marrow engraftment J Hematother 1998 7: 151–157

    Article  CAS  PubMed  Google Scholar 

  21. Marks DI, Hughes TP, Szydlo R et al. HLA-identical sibling donor bone marrow transplantation for chronic myeloid leukemia in first chronic phase: influence of GVHD prophylaxis on outcome Br J Haematol 1992 81: 383–390

    Article  CAS  PubMed  Google Scholar 

  22. Aschan J, Ringden O, Sundberg B et al. Increased risk of relapse in patients with chronic myelogenous leukemia given T-cell depleted marrow compared to methotrexate combined with cyclosporin or monotherapy for the prevention of graft-versus-host disease Eur J Haematol 1993 50: 269–274

    Article  CAS  PubMed  Google Scholar 

  23. Sehn LA, Alyea EP, Weller E et al. Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: impact of donor lymphocyte infusion J Clin Oncol 1999 17: 561–568

    Article  CAS  PubMed  Google Scholar 

  24. Drobyski WR, Hessner MJ, Klein JP et al. T-cell depletion plus salvage immunotherapy with donor leucocyte infusions as a strategy to treat chronic-phase chronic myelogenous leukemia patients undergoing HLA-identical sibling marrow transplantation Blood 1999 94: 434–441

    CAS  PubMed  Google Scholar 

  25. Verdonck LF, Peterson EJ, Lokhorst HM et al. Donor leucocyte infusions for recurrent hematologic malignancies after allogeneic bone marrow transplantation: impact of infused and residual T-cells Bone Marrow Transplant 1998 22: 1057–1063

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Mrs A Willekens and her nursing staff from the BMT-Unit for the excellent care of our patients. This work was supported by a grant from the scientific Fund W Gepts AZ-VUB.

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Schots, R., Van Riet, I., Ben Othman, T. et al. The impact of partial T cell depletion on overall transplant-related toxicity, graft function and survival after HLA-identical allogeneic bone marrow transplantation in standard risk adult patients with leukemia. Bone Marrow Transplant 28, 917–922 (2001). https://doi.org/10.1038/sj.bmt.1703268

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