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Graft-Versus-Host Disease

TLI in refractory chronic GVHD

Abstract

Refractory chronic GVHD (cGVHD) remains a major cause of morbidity after transplantation. Many drugs are used but there is no consensus on the standard of care. We investigated the efficacy of TLI in corticosteroid-refractory cGVHD. We analyzed retrospectively 31 patients receiving one or more TLI session for refractory cGVHD from 2000 to 2007. The main objective was to evaluate the response rate after TLI. Decreased corticosteroid doses and/or discontinued immunosuppressive agents were considered to be surrogate markers of response. All but one patient presented with severe cGVHD at the time of TLI. The median number of previous immunosuppressive treatment lines was 3 (range: 2–4). Fourteen patients (45%) achieved an objective response after TLI and 8 (25%) were cGVHD free at long-term follow-up. In all, 5 (29%) of the 17 nonresponsive patients did not show the features of progressive cGVHD and could decrease the amount of immunosuppressive drugs taken. Response after TLI significantly improved 5-year GVHD-related mortality (14% vs 42%, P=0.038) but not OS (58%vs 64% P=0.27). Regarding the promising response rate in this heavily pretreated population, we reasoned that TLI could be an alternative treatment for corticosteroid-refractory cGVHD.

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References

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

    Article  CAS  PubMed  Google Scholar 

  2. Sullivan KM, Weiden PL, Storb R, Witherspoon RP, Fefer A, Fisher L et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood 1989; 73: 1720–1728.

    CAS  PubMed  Google Scholar 

  3. Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED . Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 1981; 304: 1529–1533.

    Article  CAS  PubMed  Google Scholar 

  4. Socie G, Stone JV, Wingard JR, Weisdorf D, Henslee-Downey PJ, Bredeson C et al. Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry. N Engl J Med 1999; 341: 14–21.

    Article  CAS  PubMed  Google Scholar 

  5. Sullivan KM, Witherspoon RP, Storb R, Deeg HJ, Dahlberg S, Sanders JE et al. Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease. Blood 1988; 72: 555–561.

    CAS  PubMed  Google Scholar 

  6. Akpek G, Zahurak ML, Piantadosi S, Margolis J, Doherty J, Davidson R et al. Development of a prognostic model for grading chronic graft-versus-host disease. Blood 2001; 97: 1219–1226.

    Article  CAS  PubMed  Google Scholar 

  7. Martin PJ, Inamoto Y, Carpenter PA, Lee SJ, Flowers ME . Treatment of chronic graft-versus-host disease: past, present and future. Korean J Hematol 2011; 46: 153–163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Furlong T, Martin P, Flowers ME, Carnevale-Schianca F, Yatscoff R, Chauncey T et al. Therapy with mycophenolate mofetil for refractory acute and chronic GVHD. Bone Marrow Transplant 2009; 44: 739–748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Carnevale-Schianca F, Martin P, Sullivan K, Flowers M, Gooley T, Anasetti C et al. Changing from cyclosporine to tacrolimus as salvage therapy for chronic graft-versus-host disease. Biol Blood Marrow Transplant 2000; 6: 613–620.

    Article  CAS  PubMed  Google Scholar 

  10. Akpek G, Lee SM, Anders V, Vogelsang GB . A high-dose pulse steroid regimen for controlling active chronic graft-versus-host disease. Biol Blood Marrow Transplant 2001; 7: 495–502.

    Article  CAS  PubMed  Google Scholar 

  11. Cutler C, Miklos D, Kim HT, Treister N, Woo SB, Bienfang D et al. Rituximab for steroid-refractory chronic graft-versus-host disease. Blood 2006; 108: 756–762.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Magro L, Mohty M, Catteau B, Coiteux V, Chevallier P, Terriou L et al. Imatinib mesylate as salvage therapy for refractory sclerotic chronic graft-versus-host disease. Blood 2009; 114: 719–722.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bullorsky EO, Shanley CM, Stemmelin GR, Musso A, Rabinovich O, Ceresetto J et al. Total lymphoid irradiation for treatment of drug resistant chronic GVHD. Bone Marrow Transplant 1993; 11: 75–76.

    CAS  PubMed  Google Scholar 

  14. Socie G, Devergie A, Cosset JM, Pierga JY, Esperou H, Girinski T et al. Low-dose (one gray) total-lymphoid irradiation for extensive, drug-resistant chronic graft-versus-host disease. Transplantation 1990; 49: 657–658.

    Article  CAS  PubMed  Google Scholar 

  15. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  16. 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  PubMed  Google Scholar 

  17. Lee SJ, Klein JP, Barrett AJ, Ringden O, Antin JH, Cahn JY et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood 2002; 100: 406–414.

    Article  CAS  PubMed  Google Scholar 

  18. Pavletic SZ, Lee SJ, Socie G, Vogelsang G . Chronic graft-versus-host disease: implications of the National Institutes of Health consensus development project on criteria for clinical trials. Bone Marrow Transplant 2006; 38: 645–651.

    Article  CAS  PubMed  Google Scholar 

  19. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Amer Statist Assn 1958; 53: 457–481.

    Article  Google Scholar 

  20. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.

    Article  CAS  PubMed  Google Scholar 

  21. Mitchell SA, Leidy NK, Mooney KH, Dudley WN, Beck SL, LaStayo PC et al. Determinants of functional performance in long-term survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease (cGVHD). Bone Marrow Transplant 2010; 45: 762–769.

    Article  CAS  PubMed  Google Scholar 

  22. Robin M, Guardiola P, Girinsky T, Hernandez G, Esperou H, Ribaud P et al. Low-dose thoracoabdominal irradiation for the treatment of refractory chronic graft-versus-host disease. Transplantation 2005; 80: 634–642.

    Article  PubMed  Google Scholar 

  23. Wolff D, Schleuning M, von HS, Bacher U, Gerbitz A, Stadler M et al. Consensus Conference on Clinical Practice in Chronic GVHD: second-line treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant 2011; 17: 1–17.

    Article  PubMed  Google Scholar 

  24. Mohty M, Marchetti N, El-Cheikh J, Faucher C, Furst S, Blaise D . Rituximab as salvage therapy for refractory chronic GVHD. Bone Marrow Transplant 2008; 41: 909–911.

    Article  CAS  PubMed  Google Scholar 

  25. Busca A, Locatelli F, Marmont F, Ceretto C, Falda M . Recombinant human soluble tumor necrosis factor receptor fusion protein as treatment for steroid refractory graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Am J Hematol 2007; 82: 45–52.

    Article  CAS  PubMed  Google Scholar 

  26. de Lavallade H, Mohty M, Faucher C, Furst S, El-Cheikh J, Blaise D . Low-dose methotrexate as salvage therapy for refractory graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation. Haematologica 2006; 91: 1438–1440.

    PubMed  Google Scholar 

  27. Jacobsohn DA, Chen AR, Zahurak M, Piantadosi S, Anders V, Bolanos-Meade J et al. Phase II study of pentostatin in patients with corticosteroid-refractory chronic graft-versus-host disease. J Clin Oncol 2007; 25: 4255–4261.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to R Devillier.

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Devillier, R., Castagna, L., Gonzague, L. et al. TLI in refractory chronic GVHD. Bone Marrow Transplant 48, 854–858 (2013). https://doi.org/10.1038/bmt.2012.240

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