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Graft-versus-host Disease

Effective prevention of GVHD using in vivo T-cell depletion with anti-lymphocyte globulin in HLA-identical or -mismatched sibling peripheral blood stem cell transplantation

Bone Marrow Transplantation volume 49, pages 126–130 (2014)Cite this article

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Abstract

To investigate the impact of anti-lymphocyte globulin (ATG-Fresenius) as part of the HLA-sibling transplantation, we evaluated 238 patients (median age 48 years) with different diagnoses (AML, ALL, CML and lymphoproliferative disorders). A total of 79 patients received ATG and 159 patients did not. In the ATG group, there were more HLA-mismatched donors (6% vs 1%, p=0.02), bad risk patients (70% vs 55%, P=0.04), reduced intensity conditioning (RIC) regimens (65% vs 34%, P=<0.001) and older patients (median age 51 vs 48 years, P=0.002). The median time to leukocyte engraftment was significantly faster in the non-ATG group (13 vs 15 days, P < 0.001). EBV reactivation was more often seen in the ATG group (9% vs 2%, P=0.05). Cumulative incidence of acute and chronic GVHD was less observed in the ATG group (27% vs 40%, P=0.004, and 33% vs 54%, P=0.002). The cumulative incidence rates of non-relapse mortality and of relapse at 5 years were 20 and 34%, respectively, for ATG and 34 and 29%, respectively, for non-ATG (P=0.06 and P=0.3). ATG can prevent GVHD without an obvious risk of relapse but should be confirmed in a randomized study.

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References

  1. Gratwohl A, Baldomero H, Schwendener A, Gratwohl M, Apperley A, Frauendorfer K, Niederwieser D . EBMT activity survey 2008 impact of team size, team density, and new trends. Bone Marrow Transplant 2011; 46: 1–18.

    Article  Google Scholar 

  2. Friedrichs B, Tichelli A, Bacigalupo A, Russel NH, Ruutu T, Shapira MY et al. Long-term outcome and late effects in patients transplanted with mobilized blood or bone marrow: a randomized trial. Lancet Oncology 2010; 11: 331–338.

    Article  Google Scholar 

  3. Cutler C, Giri S, Jevapalan S, Paniagua D, Viswanathan A, Antin JH . 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  Google Scholar 

  4. Stem Cell Trialists‘ Collaborative Group. Allogeneic peripheral blood stem-cellcompared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials. J Clin Oncol 2005; 23: 5074–5087.

    Article  Google Scholar 

  5. Lee SJ, Kim HT, Ho VT, Cutler C, Alyea ET, Soiffer RJ et al. Quality of life associated with acute and chronic graft-versus-host disease. Bone Marrow Transplant 2006; 38: 305–310.

    Article  CAS  Google Scholar 

  6. Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med 2012; 367: 1487–1496.

    Article  CAS  Google Scholar 

  7. Zander AR, Kröger N, Schleuning M, Finke J, Zabelina T, Beelen D et al. ATG aspart of the conditioning regimen reduces transplant-related mortality (TRM) and improves overall survival after unrelated stem cell transplantation in patients with chronic myelogenous leukemia (CML). Bone Marrow Transplant 2003; 32: 355–361.

    Article  CAS  Google Scholar 

  8. Kröger N, Zabelina T, Binder T, Ayuk F, Bacher U, Amtsfeld G et al. HLA-mismatched unrelated donors as an alternative graft source for allogeneic stem cell transplantation after antithymocyte globulin-containing conditioning regimen. Biol Blood Marrow Transplant 2009; 15: 454–462.

    Article  Google Scholar 

  9. Ayuk F, Diyachenko G, Zabelina T, Wolschke C, Fehse B, Bacher U et al. Comparison of two doses of antithymocyte globulin in patients undergoing matched unrelated donor allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2008; 14: 913–919.

    Article  CAS  Google Scholar 

  10. Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander A et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors. A randomized, open-label, multicenter phase 3 trial. Lancet Oncol 2009; 10: 855–864.

    Article  CAS  Google Scholar 

  11. Bonifazi F, Bandini G, Stanzani M, Palandri F, Giannini B, Arpinato M et al. In-vivo T-cell depletion with low-dose ATG is effective in reducing cGVHD after peripheral blood stem cell myeloablative sibling transplants in CML: results from a prospective phase II study. Bone Marrow Transplant 2005; 35: 1025–1026.

    Article  CAS  Google Scholar 

  12. Kröger N, Zabelina T, Krüger W, Renges H, Stute N, Rischewski J et al. Graft-versus-host disease. In vivo T cell depletion with pretransplant antithymocyte 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  Google Scholar 

  13. Bonifazi F, Bandini G, Arpinati M, Tolomelli G, Stanzani M, Motta MR et al. Intensification of GVHD prophylaxis with low-dose ATG-F before allogeneic PBSC transplantation from HLA-identical siblings in adult patients with hematological malignancies: results from a retrospective analysis. Bone Marrow Transplant 2012; 47: 1105–1111.

    Article  CAS  Google Scholar 

  14. Przepiorka KM, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. Consensus conference on acute GVHD-grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  Google Scholar 

  15. Mohty M, Kuentz M, Michallet M, Bourhis JH, Milpied N, Sutton L et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation: long-term results of a randomized study. Blood 2002; 100: 3128–3134.

    Article  CAS  Google Scholar 

  16. Kumar A, Mhaskar AR, Reljic T, Mhaskar RS, Kharfan-Dabaja MA, Anasetti C et al. Antithymocyte globuliln for acute-graft-versus-host-disease prophylaxis in patients undergoing allogeneic hematopoietic cell transplantation: a systematic review. Leukemia 2012; 26: 582–588.

    Article  CAS  Google Scholar 

  17. Baron F, Labopin M, Niederwieser D, Vigouroux S, Cornelissen JJ, Malm C et al. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Leukemia 2012; 26: 2462–2468.

    Article  CAS  Google Scholar 

  18. Soiffer RJ, Lerademacher J, Ho V, Kan F, Artz A, Champlin RE et al. Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Blood 2011; 117: 6963–6970.

    Article  CAS  Google Scholar 

  19. Ayuk FA, Fang L, Fehse B, Zander AR, Kröger N . Antithymocyte globulin induces complement-dependent cell lysis and caspase-dependent apoptosis in myeloma cells. Exp Hematol 2005; 33: 1531–1536.

    Article  CAS  Google Scholar 

  20. Fang L, Fehse B, Engel M, Zander AR, Kröger N . Antithymocyte globulin induces ex vivo and in vivo depletion of myeloid and plasmacytoid dendritic cells. Transplantation 2005; 79: 369–371.

    Article  CAS  Google Scholar 

  21. Shimony O, Nagler A, Gellman YN, Refaeli E, Rosenblum N, Eshkar-Sebban L et al. Anti-T lymphocyte globulin (ATG) induces generation of regulatory T cells, at least part of them express activated CD44. J Clin Immunol 2012; 32: 173–188.

    Article  CAS  Google Scholar 

  22. Fehse N, Fehse B, Kröger N, Zabelina T, Freiberger P, Kruger W et al. Influence of anti-thymocyte globulin as part of the conditioning regimen on immune reconstitution following matched related bone marrow transplantation. J Hematother Stem Cell Res 2003; 12: 237–242.

    Article  Google Scholar 

  23. Eiermann TH, Lembrecht P, Zander AR . Monitoring anti-thymocyte globulin (ATG) in bone marrow recipients. Bone Marrow Transplant 1999; 23: 779–781.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Stem Cell Transplantation, University Medical Center, Hamburg, Germany

    C Wolschke, T Zabelina, F Ayuk, H Alchalby, E Klyuchnikov, U-M Pein, S Schumacher, G Amtsfeld, R Adjallé, F Wortmann, H Lellek, A Randenborgh, A Zander & N Kröger

  2. Department of Medical Statistics, University Medical Center, Hamburg, Germany

    J Berger

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  1. C Wolschke
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  2. T Zabelina
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  3. F Ayuk
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  4. H Alchalby
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  7. U-M Pein
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  9. G Amtsfeld
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  14. A Zander
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Correspondence to N Kröger.

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Author Contributions

CW wrote the manuscript; TZ and JB performed statistical analysis; FA, HA, EK, U-MP, GA, HL, SS, AR and AZ interpreted the results; and NK designed the study, analyzed the data and wrote the manuscript

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Wolschke, C., Zabelina, T., Ayuk, F. et al. Effective prevention of GVHD using in vivo T-cell depletion with anti-lymphocyte globulin in HLA-identical or -mismatched sibling peripheral blood stem cell transplantation. Bone Marrow Transplant 49, 126–130 (2014). https://doi.org/10.1038/bmt.2013.143

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