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Chronic graft-versus-host disease: where is promise for the future?

Leukemia volume 19, pages 1532–1535 (2005)Cite this article

Chronic graft-versus-host disease (GVHD) remains a troubling and dangerous complication of allogeneic stem cell transplantation with little prospect of a simple solution. The frequency of chronic GVHD over the last 12 years has increased. Data from the Fred Hutchinson Cancer Research Center indicate that in 1990, chronic GVHD incidence was about 40%; currently, the incidence is 65–80%.1, 2 This increase can be attributed to a greater number of patients surviving transplant, and to older patients being transplanted with unrelated or alternative donor grafts.2 Even though chronic GVHD may promote graft-versus-leukemia effects, large observational studies have shown that chronic GVHD is still the leading cause of nonrelapse death 2 years after transplantation.3 Patient selection plays an important role in the outcome of chronic GVHD treatment trials,4 as demonstrated by widely varying response rates to prednisone, cyclosporine, azathioprine, or combination regimens.5, 6

Chronic GVHD has been attributed to T-lymphocyte activation and overexpansion of autoreactive subsets, or both. Data from a large randomized trial in about 400 patients who received unrelated donor transplantation with either T-cell-depleted or unmodified grafts showed similar risks of chronic GVHD and nearly 20% chronic GVHD-related mortality (Pavletic SZ et al. Blood 2003; 102: 154a; abstract). This incidence is similar to that for sibling donor transplants.7, 8, 9 Only about 50% of those who developed chronic GHVD in this trial were alive at 3–4 years following the transplant. In general, neither unmodified grafts nor T-cell depletion alter the incidence of chronic GVHD or improve overall survival.

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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  Google Scholar 

  2. Akpek G, Lee SJ, Flowers ME, Pavletic SZ, Arora M, Lee S et al. Performance of a new clinical grading system for chronic graft-versus-host disease: a multicenter study. Blood 2003; 102: 802–809.

    Article  CAS  Google Scholar 

  3. 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  Google Scholar 

  4. Lee SJ, Vogelsang G, Gilman A, Weisdorf DJ, Pavletic S, Antin JH et al. A survey of diagnosis, management, and grading of chronic GVHD. Biol Blood Marrow Transplant 2002; 8: 32–39.

    Article  Google Scholar 

  5. Sullivan KM, Shulman HM, Storb R, Weiden PL, Witherspoon RP, McDonald GB et al. Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood 1981; 57: 267–276.

    CAS  PubMed  Google Scholar 

  6. 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 

  7. Keever-Taylor CA, Bredeson C, Loberiza FR, Casper JT, Lawton C, Rizzo D 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 

  8. Irschick EU, Hladik F, Niederwieser D, Nussbaumer W, Holler E, Kaminski E et al. Studies on the mechanism of tolerance or graft-versus-host disease in allogeneic bone marrow recipients at the level of cytotoxic T-cell precursor frequencies. Blood 1992; 79: 1622–1628.

    CAS  PubMed  Google Scholar 

  9. Ochs LA, Miller WJ, Filipovich AH, Haake RJ, McGlave PB, Blazar BR et al. Predictive factors for chronic graft-versus-host disease after histocompatible sibling donor bone marrow transplantation. Bone Marrow Transplant 1994; 13: 455–460.

    CAS  PubMed  Google Scholar 

  10. Kansu E, Gooley T, Flowers ME, Anasetti C, Deeg HJ, Nash RA et al. Administration of cyclosporine for 24 months compared with 6 months for prevention of chronic graft-versus-host disease: a prospective randomized clinical trial. Blood 2001; 98: 3868–3870.

    Article  CAS  Google Scholar 

  11. Storb R, Leisenring W, Anasetti C, Applebaum FR, Deeg HJ, Doney K et al. Methotrexate and cyclosporine for graft-vs-host disease prevention: what length of therapy with cyclosporine? Biol Blood Marrow Transplant 1997; 3: 194–201.

    CAS  PubMed  Google Scholar 

  12. Arora M, Wagner JE, Davies SM, Blazar BR, Defor T, Enright H et al. Randomized clinical trial of thalidomide, cyclosporine, and prednisone vs cyclosporine and prednisone as initial therapy for chronic graft-versus-host disease. Biol Blood Marrow Transplant 2001; 7: 265–273.

    Article  CAS  Google Scholar 

  13. Browne PV, Weisdorf DJ, DeFor T, Miller WJ, Davies SM, Filipovich A et al. Response to thalidomide therapy in refractory chronic graft-versus-host disease. Bone Marrow Transplant 2000; 26: 865–869.

    Article  CAS  Google Scholar 

  14. Koga Y, Nagatoshi Y, Kawano Y, Okamura J . Methotrexate vs cyclosporin A as a single agent for graft-versus-host disease prophylaxis in pediatric patients with hematological malignancies undergoing allogeneic bone marrow transplantation from HLA-identical siblings: a single-center analysis in Japan. Bone Marrow Transplant 2003; 32: 171–176.

    Article  CAS  Google Scholar 

  15. Winston DJ, Antin JH, Wolff SN, Bierer BE, Small T, Miller KB et al. A multicenter, randomized, double-blind comparison of different doses of intravenous immunoglobulin for prevention of graft-versus-host disease and infection after allogeneic bone marrow transplantation. Bone Marrow Transplant 2001; 28: 187–196.

    Article  CAS  Google Scholar 

  16. Lee SJ, Loberiza FR, Rizzo JD, Soiffer RJ, Antin JH, Weeks JC . Optimistic expectations and survival after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2003; 9: 389–396.

    Article  Google Scholar 

  17. Arora M, Burns LJ, Davies SM, MacMillan ML, DeFor TE, Miller WJ et al. Chronic graft-versus-host disease: a prospective cohort study. Biol Blood Marrow Transplant 2003; 9: 38–45.

    Article  Google Scholar 

  18. 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  Google Scholar 

  19. Koc S, Leisenring W, Flowers ME, Anasetti C, Deeg HJ, Nash RA et al. Therapy for chronic graft-versus-host disease: a randomized trial comparing cyclosporine plus prednisone vs prednisone alone. Blood 2002; 100: 48–51.

    Article  CAS  Google Scholar 

  20. Johnston LJ, Brown J, Shizura JA, Stockerl-Goldstein KE, Stuart MJ, Blume KG et al. Rapamycin (sirolimus) for treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant 2005; 11: 47–55.

    Article  CAS  Google Scholar 

  21. Apisarnthanarax N, Donato M, Korbling M, Couriel D, Gajewski J, Giralt S et al. Extracorporeal photopheresis therapy in the management of steroid-refractory or steroid-dependent cutaneous chronic graft-versus-host disease after allogeneic stem cell transplantation: feasibility and results. Bone Marrow Transplant 2003; 31: 459–465.

    Article  CAS  Google Scholar 

  22. Bisaccia E, Gonzalez J, Palangio M, Schwartz J, Klainer AS . Extracorporeal photochemotherapy alone or with adjuvant therapy in the treatment of cutaneous T-cell lymphoma: a 9-year retrospective study at a single institution. J Am Acad Dermatol 2000; 43: 263–271.

    Article  CAS  Google Scholar 

  23. De Jesus J, Ghosh S, Hsu Y, Neuman J, Cohen A, Champlin R et al. Tacrolimus in combination with steroids for the treatment of chronic GVHD. Biol Bone Marrow Transplant 2004; 10 (Suppl): 49.

    Article  Google Scholar 

  24. Mohty M, de Lavallade H, Faucher C, Bilger K, Vey N, Stoppa AM et al. Mycophenolate mofetil and cyclosporine for graft-versus-host disease prophylaxis following reduced intensity conditioning allogeneic stem cell transplantation. Bone Marrow Transplant 2004; 34: 527–530.

    Article  CAS  Google Scholar 

  25. Kasper C, Sayer HG, Mugge LO, Schilling K, Scholl S, Issa MC et al. Combined standard graft-versus-host disease (GvHD) prophylaxis with mycophenolate mofetil (MMF) in allogeneic peripheral blood stem cell transplantation from unrelated donors. Bone Marrow Transplant 2004; 33: 65–69.

    Article  CAS  Google Scholar 

  26. Kim JG, Sohn SK, Kim DH, Lee NY, Suh JS, Lee KS et al. Different efficacy of mycophenolate mofetil as salvage treatment for acute and chronic GVHD after allogeneic stem cell transplant. Eur J Haematol 2004; 73: 56–61.

    Article  CAS  Google Scholar 

  27. Kulkarni S, Powles R, Sirohi B, Treleaven J, Saso R, Horton C et al. Thalidomide after allogeneic haematopoietic stem cell transplantation: activity in chronic but not in acute graft-versus-host disease. Bone Marrow Transplant 2003; 32: 165–170.

    Article  CAS  Google Scholar 

  28. Farag SS . Chronic graft-versus-host disease: where do we go from here? Bone Marrow Transplant 2004; 33: 569–577.

    Article  CAS  Google Scholar 

  29. Khoury H, Trinkaus K, Zhang MJ, Adkins D, Brown R, Vij R et al. Hydroxychloroquine for the prevention of acute graft-versus-host disease after unrelated donor transplantation. Biol Blood Marrow Transplant 2003; 9: 714–721.

    Article  CAS  Google Scholar 

  30. Lee SJ, Wegner SA, McGarigle CJ, Bierer BE, Antin JH . Treatment of chronic graft-versus-host disease with clofazimine. Blood 1997; 89: 2298–2302.

    CAS  PubMed  Google Scholar 

  31. Marcellus DC, Altomonte VL, Farmer ER, Horn TD, Freemer CS, Grant J et al. Etretinate therapy for refractory sclerodermatous chronic graft-versus-host disease. Blood 1999; 93: 66–70.

    CAS  PubMed  Google Scholar 

  32. Grundmann-Kollmann M, Martin H, Ludwig R, Klein S, Boehncke WH, Hoelzer D et al. Narrowband UV-B phototherapy in the treatment of cutaneous graft versus host disease. Transplantation 2002; 74: 1631–1634.

    Article  CAS  Google Scholar 

  33. Chiang KY, Abhyankar S, Bridges K, Godder K, Henslee-Downey JP . Recombinant human tumor necrosis factor receptor fusion protein as complementary treatment for chronic graft-versus-host disease. Transplantation 2002; 73: 665–667.

    Article  CAS  Google Scholar 

  34. Couriel D, Saliba R, Hicks K, Ippoliti C, de Lima M, Hosing C et al. Tumor necrosis factor-alpha blockade for the treatment of acute GVHD. Blood 2004; 104: 649–654.

    Article  CAS  Google Scholar 

  35. Przepiorka D, Kernan NA, Ippoliti C, Papadopoulos EB, Giralt S, Khouri I et al. Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood 2000; 95: 83–89.

    CAS  PubMed  Google Scholar 

  36. Lee SJ, Chakrabarti S, Walsh T, Igarashi T, Takahashi Y, Kleiner D et al. Improved survival in steroid-refractory acute graft versus host disease after non-myeloablative allogeneic transplantation using a daclizumab-based strategy with comprehensive infection prophylaxis. Br J Haematol 2004; 124: 777–786.

    Article  Google Scholar 

  37. 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 

  38. Canninga-Van Dijk MR, Van Der Straaten HM, Fijnheer R, Sanders CJ, Van Den Tweel JG, Verdonck LF . Anti-CD20 monoclonal antibody treatment in 6 patients with therapy-refractory chronic graft-versus-host disease. Blood 2004; 104: 2603–2606.

    Article  CAS  Google Scholar 

  39. Vogelsang GB . How I treat chronic graft-versus-host disease. Blood 2001; 97: 1196–1201.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Blood and Marrow Transplantation Program, University of Minnesota, Minneapolis, MN, USA

    D J Weisdorf

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Correspondence to D J Weisdorf.

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This paper is part of a series of keynote addresses to be published in Leukemia. They were presented at the Acute Leukemia Forum San Francisco, Friday April 16, 2004

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Weisdorf, D. Chronic graft-versus-host disease: where is promise for the future?. Leukemia 19, 1532–1535 (2005). https://doi.org/10.1038/sj.leu.2403856

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