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Graft-Versus-Host Disease

Pre-transplantation risk factors to develop sclerotic chronic GvHD after allogeneic HSCT: A multicenter retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

Bone Marrow Transplantation volume 50, pages 253–258 (2015)Cite this article

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Abstract

Sclerotic chronic GvHD (cGvHD) is one of the most severe complications after allo-hematopoietic stem cell transplantation (HSCT). Risk factors associated with this complication remain not very well defined. With the aim to define a pre-transplantation risk profile, we have conducted a French retrospective analysis in 705 consecutive patients between 2005 and 2010. Analyses to determine pre-transplantation risk factors included as variables: patient and donor age, kind of donor, HLA matching, ABO matching, sex-matching, diagnosis, stem cell source, gender, GvHD prophylaxis and antithymocyte globulin (ATG) in the conditioning regimen. The cumulative incidence of sclerotic cGvHD was 18% (95% CI, 16.6–19.6) 3 years after onset of cGvHD. In univariate analysis, we found a significantly lower number of sclerotic cGvHD form in patients transplanted from cord blood cells (P=0.0021), in patients with a one mismatched donor (P=0.041) and in patients who had received ATG in the conditioning regimen (P=0.002). In multivariate analysis, factors associated with an increased risk of sclerotic cGvHD were young patient age, multiple myeloma and PBSC as the stem cell source. ATG in conditioning regimen and cord blood unit as the stem cell source were associated with a lower risk.

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References

  1. Gratwohl AA, Moutsopoulos HM, Chused TM, Akizuki M, Wolf RO, Sweet JB et al. Sjogren-type syndrome after allogeneic bone-marrow transplantation. Ann Intern Med 1977; 87: 703–706.

    Article  CAS  Google Scholar 

  2. Shulman HM, Kleiner D, Lee SJ, Morton T, Pavletic SZ, Farmer E et al. Histopathologic diagnosis of chronic graft-versus- host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. Pathology Working Group Report. Biol Blood Marrow Transplant 2006; 12: 31–47.

    Article  Google Scholar 

  3. Chosidow O, Bagot M, Vernant JP, Roujeau JC, Cordonnier C, Kuentz M et al. Sclerodermatous chronic graft-versus-host disease. Analysis of seven cases. J Am Acad Dermatol 1992; 26: 49–55.

    Article  CAS  Google Scholar 

  4. Skert C, Patriarca F, Sperotto A, Cerno M, Fili C, Zaja F et al. Sclerodermatous chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: incidence, predictors and outcome. Haematologica 2006; 91: 258–261.

    PubMed  Google Scholar 

  5. Jedlickova Z, Burlakova I, Bug G, Baurmann H, Schwerdtfeger R, Schleuning M . Therapy of sclerodermatous chronic graft-versus-host disease with mammalian target of rapamycin inhibitors. Biol Blood Marrow Transplant 2011; 17: 657–663.

    Article  CAS  Google Scholar 

  6. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956.

    Article  Google Scholar 

  7. Martires KJ, Baird K, Steinberg SM, Grkovic L, Joe GO, Williams KM et al. Sclerotic-type chronic GVHD of the skin: clinical risk factors, laboratory markers, and burden of disease. Blood 2011; 118: 4250–4257.

    Article  CAS  Google Scholar 

  8. Inamoto Y, Storer BE., Petersdorf EW., Nelson JL, Lee SJ, Carpenter PA et al. Incidence, risk factors and outcomes of sclerosis in patients with chronic graft-versus-host disease. Blood 2013; 121: 5098–5103.

    Article  CAS  Google Scholar 

  9. Flowers ME, Inamoto Y, Carpenter PA, Lee SJ, Kiem HP, Petersdorf EW et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood 2011; 117: 3214–3219.

    Article  CAS  Google Scholar 

  10. Vigorito AC, Campregher PV, Storer BE, Carpenter PA, Moravec CK, Kiem HP et al. Evaluation of NIH consensus criteria for classification of late acute and chronic GVHD. Blood 2009; 114: 702–708.

    Article  CAS  Google Scholar 

  11. Fine JP, Gray RJ . A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496–509.

    Article  Google Scholar 

  12. Arora M, Klein JP, Weisdorf DJ, Hassebroek A, Flowers ME, Cutler CS et al. Chronic GVHD risk score: a Center for International Blood and Marrow Transplant Research analysis. Blood 2011; 117: 6714–6720.

    Article  CAS  Google Scholar 

  13. Ringden O, Paulin T, Lonnqvist B, Nilsson B . Analysis of factors predisposing to chronic graft-versus-host disease. Exp Hematol 1985; 13: 1062–1067.

    CAS  PubMed  Google Scholar 

  14. Lee SJ, Vogelsang G, Flowers ME . Chronic graft-versus-host disease. Biol Blood Marrow Transplant 2003; 9: 215–233.

    Article  CAS  Google Scholar 

  15. Gabrielli A, Avvedimento EV, Krieg T . Scleroderma. N Engl J Med 2009; 360: 1989–2003.

    Article  CAS  Google Scholar 

  16. Gay S, Jones RE Jr, Huang GQ . Immunohistologic demonstration of platelet-derived growth factor (PDGF) and sis-oncogene in scleroderma. J Invest Dermatol 1989; 92: 301–303.

    Article  CAS  Google Scholar 

  17. Banovic T, MacDonald KP, Morris ES, Rowe V, Kuns R, Don A et al. TGF-beta in allogeneic stem cell transplantation: friend or foe?. Blood 2005; 106: 2206–2214.

    Article  CAS  Google Scholar 

  18. Zhang Y, McCormick LL, Gilliam AC . Latency- associated peptide prevents skin fibrosis in mu- rine sclerodermatous graft-versus-host disease, a model for human scleroderma. J Invest Dermatol 2003; 121: 713–719.

    Article  CAS  Google Scholar 

  19. Cutler C, Giri S, Jeyapalan 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 

  20. Mohty M, Bilger K, Jourdan E, Kuentz M, Michallet M, Bourhis JH et al. Higher doses of CD34+ peripheral blood stem cells are associated with increased mortality from chronic graft-versus-host disease after allogeneic HLA-identical sibling transplantation. Leukemia 2003; 17: 869–875.

    Article  CAS  Google Scholar 

  21. 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 

  22. Hill GR, Olver SD, Kuns RD, Varelias A, Raffelt NC, Don AL et al. Stem cell mobilization with G-CSF induces type 17 differentiation and promotes scleroderma. Blood 2010; 116: 819–828.

    Article  CAS  Google Scholar 

  23. Björkstrand B, Iacobelli S, Hegenbart U, Gruber A, Greinix H, Volin L et al. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up. J Clin Oncol 2011; 29: 3016–3022.

    Article  Google Scholar 

  24. Bacigalupo A, Lamparelli T, Barisione G, Bruzzi P, Guidi S, Alessandrino PE et al. Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. Biol Blood Marrow Transplant 2006; 12: 560–565.

    Article  Google Scholar 

  25. Socie G, Schmoor C, Bethge WA, Ottinger HD, Stelljes M, Zander AR et al. Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius. Blood 2011; 117: 6375–6638.

    Article  CAS  Google Scholar 

  26. Mohty M, Labopin M, Balère ML, Socie G, Milpied N, Tabrizi R et al. Antithymocyte globulins and chronic graft-vs-host disease after myeloablative allogeneic stem cell transplantation from HLA-matched unrelated donors: a report from the Sociéte Française de Greffe de Moelle et de Thérapie Cellulaire. Leukemia 2010; 24: 1867–1874.

    Article  CAS  Google Scholar 

  27. Na IK, Lu SX, Yim NL, Goldberg GL, Tsai J, Rao U et al. The cytolytic molecules Fas ligand and TRAIL are required for murine thymic graft-versus-host disease. J Clin Invest 2010; 120: 343–356.

    Article  CAS  Google Scholar 

  28. Feng X, Kajigaya S, Solomou EE, Keyvanfar K, Xu X, Raghavachari N et al. Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro. Blood 2008; 111: 3675–3683.

    Article  CAS  Google Scholar 

  29. Ponce DM, Gonzales A, Lubin M, Castro-Malaspina H, Giralt S, Goldberg JD. et al. Graft-versus-host disease after double-unit cord blood transplantation has unique features and an association with engrafting unit-to-recipient HLA match. Biol Blood Marrow Transplant 2013; 19: 904–911.

    Article  CAS  Google Scholar 

  30. Milano F, Delaney C, Storb R . Graft-versus-host-disease after double cord blood transplantation: a new look at its characteristics. Biol Blood Marrow Transplant 2013; 19: 847–848.

    Article  Google Scholar 

  31. Ratanatharathorn V, Ayash L, Reynolds C, Silver S, Reddy P, Becker M et al. Treatment of chronic graft-versus-host disease with anti-CD20 chimeric monoclonal antibody. Biol Blood Marrow Transplant 2003; 9: 505–511.

    Article  CAS  Google Scholar 

  32. Magro L, Catteau B, Coiteux V, Bruno B, Jouet JP, Yakoub-Agha I . Efficacy of imatinib mesylate in the treatment of refractory sclerodermatous chronic GvHD. Bone Marrow Transplant 2008; 42: 757–760.

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank the members of the Société Française de Greffe de Moelle et de Thérapie cellulaire (SFGM-TC), the SFGM-TC data manager Nicole Raus and all collaborators who contributed to patient recruitment, data registration and quality control of the study. Marie Detrait would like to thank François Duhoux (MD,PhD) for the reading of the manuscript and advices.

Author Contributions

MD designed the study, collected and analyzed data, and wrote the manuscript. SM performed the statistical analysis and contributed to the redaction of the manuscript. MD and FB; RPL; IYA and LM; RC; RT and SV; JOB and PC completed questionnaires for their centers. RPL and GS; FB, MD and MM; IYA and LM; RC and DB; RT, SV and NM; JOB; PC and MMo were the principal contributors of clinical data from the seven centers. NR sent data capture forms to the centers, collected clinical data from questionnaires and performed the extraction of clinical data. MM has been the supervisor of the study. RPdL, RC, FB, MMo, NM and GS read and commented on the manuscript.

Author information

Authors and Affiliations

  1. Hematology Department, Groupement Hospitalier Sud, Hospices Civils de Lyon, Université Claude Bernard Lyon EST, Pierre Bénite, France

    M Y Detrait, F Barraco & M Michallet

  2. Department of Hematology, Biostatistician, Clinical Research Unit, Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre Bénite, France

    S Morisset

  3. Blood and Marrow Transplantation Unit,Hôpital Saint-Louis, AP-HP, Paris, France

    R Peffault de Latour & G Socié

  4. Service des Maladies du Sang, CHU Lille, Lille, France

    I Yakoub-Agha & L Magro

  5. Hematology Department, Blood and marrow transplantation Program, Institut Paoli-Calmettes, Marseille, France

    R Crocchiolo & D Blaise

  6. Hematology Department, Hôpital du Haut Levêque, Pessac, France

    R Tabrizi, S Vigouroux & N Milpied

  7. Hematology Department, CHU Clermont-Ferrand, Hôpital Estaing, Clermont-Ferrand, France

    J-O Bay

  8. Hematology Department, Center Hospitalier Universitaire (CHU) de Nantes, Nantes, France

    P Chevalier & M Mohty

  9. Data management of SFGM-TC, Centre Hospitalier Lyon Sud, Pierre-Bénite, France

    N Raus

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  1. M Y Detrait
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  11. S Vigouroux
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  14. N Milpied
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  16. G Socié
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Corresponding author

Correspondence to M Y Detrait.

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The authors declare no conflict of interest.

Additional information

This study was presented as an oral session during the 39th Annual Meeting of the European Group for Blood and Marrow Transplantation in London, UK, April 7–10, 2013 (Bone Marrow Transplant April 2013; Vol 48 (Supp2): S1-S574 (abstract 0326)).

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Detrait, M., Morisset, S., Peffault de Latour, R. et al. Pre-transplantation risk factors to develop sclerotic chronic GvHD after allogeneic HSCT: A multicenter retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). Bone Marrow Transplant 50, 253–258 (2015). https://doi.org/10.1038/bmt.2014.244

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