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Post-Transplant Events

Prognostic value of T-1 cell numbers prior to allogeneic stem cell transplantation in patients with severe graft-versus-host disease

Bone Marrow Transplantation volume 35, pages 691–697 (2005)Cite this article

Summary:

Assessment of risk factors for acute graft-versus-host disease (aGvHD) might help in tailoring the intensity of prophylactic immunosuppression after allogeneic stem cell transplantation (SCT), thereby decreasing the relapse rate in leukaemia patients. In this study, we analysed whether the number of recipient blood T cells and plasma levels of different cytokines were correlated with the risk of aGvHD after allogeneic SCT. Analyses were performed in 23 patients receiving pSCT immediately before or during the first 2 days of the conditioning regimen. In all, 40 or more Tc-1 cells/μl pretransplant were associated with a significantly increased risk of aGvHD (10/10 patients with GvHD⩾II; 4/13 patients without aGvHD with a Tc-1 number >40/μl, P<0.002, Fisher's exact test). In addition, 40 or more Th-1 cells/μl pretransplant were also associated with a significantly increased risk of aGvHD (P<0.04, Fisher's exact test). Furthermore, the number of Th-2 cells was significantly higher in patients with severe aGvHD even though the median absolute cell counts were very low. However, all other investigated parameters did not reveal predictive value. In conclusion, determination of T-1 cells prior to SCT might determine patients with high/low risk of aGvHD and could thus be used to control immunosuppression after SCT.

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References

  1. Bertz H, Illerhaus G, Veelken H, Finke J . Allogeneic hematopoietic stem-cell transplantation for patients with relapsed or refractory lymphomas: comparison of high-dose conventional conditioning versus fludarabine-based reduced-intensity regimens. Ann Oncol 2002; 13: 135–139.

    Article  CAS  Google Scholar 

  2. Borgmann A, von Stackelberg A, Hartmann R et al. Unrelated donor stem cell transplantation compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission: a matched-pair analysis. Blood 2003; 101: 3835–3839.

    Article  CAS  Google Scholar 

  3. Yumura-Yagi K, Hara J, Horibe K et al. Outcome after relapse in childhood acute lymphoblastic leukemia. Int J Hematol 2002; 76: 61–68.

    Article  Google Scholar 

  4. Barrett J . Allogeneic stem cell transplantation for chronic myeloid leukemia. Semin Hematol 2003; 40: 59–71.

    Article  Google Scholar 

  5. Gilleece MH, Dazzi F . Donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukaemia. Leuk Lymphoma 2003; 44: 23–28.

    Article  Google Scholar 

  6. Hassan IA, Chopra R, Swindell R, Mutton KJ . Respiratory viral infections after bone marrow/peripheral stem-cell transplantation: the Christie hospital experience. Bone Marrow Transplant 2003; 32: 73–77.

    Article  CAS  Google Scholar 

  7. Daly A, McAfee S, Dey B et al. Nonmyeloablative bone marrow transplantation: infectious complications in 65 recipients of HLA-identical and mismatched transplants. Biol Blood Marrow Transplant 2003; 9: 373–382.

    Article  Google Scholar 

  8. Bonig H, Schneider DT, Sprock I et al. Sepsis' and multi-organ failure: predictors of poor outcome after hematopoietic stem cell transplantation in children. Bone Marrow Transplant 2000; 25 (Suppl. 2): S32–S34.

    Article  Google Scholar 

  9. Pastores SM, Papadopoulos E, van den Brink M et al. Septic shock and multiple organ failure after hematopoietic stem cell transplantation: treatment with recombinant human activated protein C. Bone Marrow Transplant 2002; 30: 131–134.

    Article  CAS  Google Scholar 

  10. Martino R, Giralt S, Caballero MD et al. Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning in acute lympho-blastic leukemia: a feasibility study. Haematologica 2003; 88: 555–560.

    Google Scholar 

  11. Georges GE, Maris M, Sandmaier BM et al. Related and unrelated nonmyeloablative hematopoietic stem cell transplantation for malignant diseases. Int J Hematol 2002; 76 (Suppl. 1): 184–189.

    Article  Google Scholar 

  12. Cavet J, Middleton PG, Segall M et al. Recipient tumor necrosis factor-α and interleukin-10 gene polymorphisms associate with early mortality and acute graft-versus-host disease severity in HLA-matched sibling bone marrow transplants. Blood 1999; 94: 3914–3946.

    Google Scholar 

  13. Holler E, Roncarolo MG, Hintermeier-Knabe R et al. Prognostic significance of increased IL-10 production in patients prior to allogeneic bone marrow transplantation. Bone Marrow Transplant 2000; 25: 237–241.

    Article  CAS  Google Scholar 

  14. Sykes M . Novel approaches to the control of graft versus host disease. Curr Opin Immunol 1993; 5: 774–781.

    Article  CAS  Google Scholar 

  15. Rus V, Svetic A, Nguyen P et al. Kinetics of Th1 and Th2 cytokine production during the early course of acute and chronic murine graft-versus-host disease. Regulatory role of donor CD8+ T cells. J Immunol 1995; 155: 2396–3406.

    CAS  Google Scholar 

  16. Love KS, Lakshmanan RR, Butterfield JH, Fox CC . IFN-gamma-stimulated enhancement of MHC class II antigen expression by the human mast cell line HMC-1. Cell Immunol 1996; 170: 85–90.

    Article  CAS  Google Scholar 

  17. Niederwieser D, Aubock J, Troppmair J et al. IFN-mediated induction of MHC antigen expression on human keratinocytes and its influence on in vitro alloimmune responses. J Immunol 1988; 140: 2556–2564.

    CAS  PubMed  Google Scholar 

  18. Banning U, Korholz D . Intracellular detection of T-cell cytokines. Differentiation of TH1 and TH2 cells. In: Kiess W, Korholz D (eds). Methods in Molecular Biology. Humana Press: Totowa, New Jersey, Vol 215, 2003, pp 15–22.

    Google Scholar 

  19. 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  Google Scholar 

  20. Kollman C, Howe CW, Anasetti C et al. Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood 2001; 98: 2043–2051.

    Article  CAS  Google Scholar 

  21. Keever-Taylor CA, Bredeson C, Loberiza FR et al. Analysis of risk factors for the development of GVHD after T cell-depleted allogeneic BMT: effect of HLA disparity, ABO incompatibility, and method of T-cell depletion. Biol Blood Marrow Transplant 2001; 7: 620–630.

    Article  CAS  Google Scholar 

  22. Goker H, Haznedaroglu IC, Chao NJ . Acute graft-vs-host disease: pathobiology and management. Exp Hematol 2001; 29: 259–277.

    Article  CAS  Google Scholar 

  23. Banna GL, Aversa S, Sileni VC et al. Nonmyeloablative allogeneic stem cell transplantation (NST) after truly nonmyeloablative and reduced intensity conditioning regimens. Crit Rev Oncol 2004; 51: 171–189.

    Article  Google Scholar 

  24. Morishima Y, Sasazuki T, Inoko H et al. The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors. Blood 2002; 99: 4200–4206.

    Article  CAS  Google Scholar 

  25. Eskdale J, Gallagher G, Verweij CL et al. Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acad Sci USA 1998; 95: 9465–9470.

    Article  CAS  Google Scholar 

  26. Bejarano MT, de Waal Malefyt R, Abrams JS et al. Interleukin 10 inhibits allogeneic proliferative and cytotoxic T cell responses generated in primary mixed lymphocyte cultures. Int Immunol 1992; 4: 1389–1397.

    Article  CAS  Google Scholar 

  27. Korholz D, Banning U, Bonig H et al. The role of interleukin-10 (IL-10) in IL-15-mediated T-cell responses. Blood 1997; 90: 4513–4521.

    CAS  PubMed  Google Scholar 

  28. Niederwieser D, Herold M, Woloszczuk W et al. Endogenous IFN-gamma during human bone marrow transplantation. Analysis of serum levels of interferon and interferon-dependent secondary messages. Transplantation 1990; 50: 620–625.

    Article  CAS  Google Scholar 

  29. De Maeyer E, De Maeyer-Guignard J . Interferons. In: Thomson A (ed.). The Cytokine Handbook. Academic press: San Diego, 1998, pp 491–516.

    Google Scholar 

  30. Weiden PL, Doney K, Storb R, Thomas ED . Anti-human thymocyte globulin for prophylaxis and treatment of graft-versus-host disease in recipients of allogeneic marrow graft. Transplant Proc 1978; 10: 213–216.

    CAS  PubMed  Google Scholar 

  31. Doney KC, Weiden PL, Storb R, Thomas ED . Treatment of graft-versus-host disease in human allogeneic marrow graft recipients: a randomised trial comparing antithymocyte globulin and corticosteroids. Am J Hematol 1981; 11: 1–8.

    Article  CAS  Google Scholar 

  32. Deeg HJ, Loughran Jr TP, Storb R et al. Treatment of acute graft-versus-host disease with antithymocyte globulin and cyclosporine with or without methylprednisolone. Transplantation 1985; 40: 162–166.

    Article  CAS  Google Scholar 

  33. Dugan MJ, DeFor TE, Steinbuch M et al. ATG plus corticosteroid therapy for acute graft-versus-host disease: predictors of response and survival. Ann Hematol 1997; 75: 41–46.

    Article  CAS  Google Scholar 

  34. Cragg L, Blazar BR, Defor T et al. A randomised trial comparing prednisone with antithymocyte globulin/prednisone as an initial systemic therapy for moderately severe acute graft-versus-host disease. Biol Blood Marrow Transplant 2000; 6: 441–447.

    Article  CAS  Google Scholar 

  35. Remberger M, Aschan J, Barkholt L et al. Treatment of severe acute graft-versus-host disease with anti-thymocyte globulin. Clin Transplantation 2001; 15: 147–153.

    Article  CAS  Google Scholar 

  36. Bonig H, Korholz D, Lex C et al. Monocyte deactivation and ist reversal in a patient with chemotherapy-induced leukopenia and severe systemic infection. Med Pediatr Oncol 2000; 34: 39–42.

    Article  CAS  Google Scholar 

  37. Wong GH, Clark-Lewis I, McKimm-Breschkin L et al. Interferon-gamma induces enhanced expression of Ia and H-2 antigens on b lymphoid, macrophage, and myeloid cell lines. J Immunol 1983; 131: 788–793.

    CAS  PubMed  Google Scholar 

  38. Ito T, Amakawa R, Inaba M et al. Differential regulation of human blood dendritic cell subsets by IFNs. J Immunol 2001; 166: 2961–2969.

    Article  CAS  Google Scholar 

  39. Anderson BE, McNiff JM, Jain D et al. Distinct roles for donor- and host-derived antigen presenting cells and costimulatory molecules in murine chronic graft versus host disease: requirements depend on target organ. Blood First Edition Paper, prepublished online November 2, 2004, DOI 10. 1182/blood-2004-08-3032.

  40. Storkus WJ, Tahara H, Lotze MT . Interleukin-12. In: Thomson AW (ed.). The Cytokine Handbook. Academic Press: San Diego, CA, 1998, pp 391–426.

    Google Scholar 

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Acknowledgements

We thank HD Foss and colleagues for their help with the IP-10 ELISA. U Banning was supported by a grant from Deutsche Krebshilfe. C Mauz-Körholz was supported by grants from Hand-in-Hand for Children and Peter-Escher Foundation.

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Authors and Affiliations

  1. Division of Paediatric Hematology, Oncology and Hemostaseology, Clinic for Children and Adolescents, University of Leipzig Medical Center, Leipzig, Germany

    U Banning, C Mauz-Körholz & D Körholz

  2. Division of Hematology and Oncology, Department of Internal Medicine, University of Leipzig Medical Centre, Leipzig, Germany

    T Lange, R Krahl & D Niederwieser

  3. Institut für umweltmedizinische Forschung (IUF), Heinrich-Heine-University Duesseldorf gGmbH, Duesseldorf, Germany

    J Krutmann

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  1. U Banning
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Correspondence to U Banning.

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Banning, U., Lange, T., Krahl, R. et al. Prognostic value of T-1 cell numbers prior to allogeneic stem cell transplantation in patients with severe graft-versus-host disease. Bone Marrow Transplant 35, 691–697 (2005). https://doi.org/10.1038/sj.bmt.1704874

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