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Graft-versus-Host Disease

Efficacy of imatinib mesylate in the treatment of refractory sclerodermatous chronic GVHD

Bone Marrow Transplantation volume 42, pages 757–760 (2008)Cite this article

Abstract

Treatment of sclerodermatous chronic GVHD (cGVHD) remains disappointing. Imatinib mesylate enables selective, dual inhibition of the transforming growth factor β (TGFβ) and PDGF pathways. Recently, the drug's effects on fibroblasts have been reported in both in vitro and in vivo studies. The inhibition of fibroblast growth and decreased collagen production in dermal fibroblasts is thus a logical therapeutic approach. Two patients who developed refractory sclerodermatous cGVHD following allo-SCT received imatinib mesylate at the dose of 400 mg/day. In both patients, the scleroderma symptoms disappeared within 3 months of initiation of the treatment. At the time of this report, the two patients were both alive and had a very good skin response. This report shows that imatinib is effective in patients with refractory sclerodermatous cGVHD. Considering its well-documented clinical profile in other diseases, imatinib is a promising candidate for the treatment of sclerodermatous cGVHD.

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References

  1. Suciu S, Mandelli F, de Witte T, Zittoun R, Gallo E, Labar B et al. Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial. Blood 2003; 102: 1232–1240.

    Article  CAS  PubMed  Google Scholar 

  2. Hunault M, Harousseau JL, Delain M, Truchan-Graczyk M, Cahn JY, Witz F et al. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood 2004; 104: 3028–3037.

    Article  CAS  PubMed  Google Scholar 

  3. Sanders JE, Im HJ, Hoffmeister PA, Gooley TA, Woolfrey AE, Carpenter PA et al. Allogeneic hematopoietic cell transplantation for infants with acute lymphoblastic leukemia. Blood 2005; 105: 3749–3756.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Micol JB, Berthon C, Tricot S, Terriou L, Darre S, Cracco P et al. Allogeneic stem-cell transplantation with fludarabine and 2-Gy TBI-based conditioning regimen for chronic hematological malignancy: a study of 25 consecutive patients and a literature review. Leuk Lymphoma 2007; 48: 321–329.

    Article  CAS  PubMed  Google Scholar 

  5. Yakoub-Agha I, de La Salmoniere P, Ribaud P, Sutton L, Wattel E, Kuentz M et al. Allogeneic bone marrow transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia: a long-term study of 70 patients-report of the French society of bone marrow transplantation. J Clin Oncol 2000; 18: 963–971.

    Article  CAS  PubMed  Google Scholar 

  6. Baudard M, Vincent A, Moreau P, Kergueris MF, Harousseau JL, Milpied N . Mycophenolate mofetil for the treatment of acute and chronic GVHD is effective and well tolerated but induces a high risk of infectious complications: a series of 21 BM or PBSC transplant patients. Bone Marrow Transplant 2002; 30: 287–295.

    Article  CAS  PubMed  Google Scholar 

  7. 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 

  8. 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 

  9. Giralt SA, Arora M, Goldman JM, Lee SJ, Maziarz RT, McCarthy PL et al. Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia. Br J Haematol 2007; 137: 461–467.

    Article  CAS  PubMed  Google Scholar 

  10. O′Brien SG, Deininger MW . Imatinib in patients with newly diagnosed chronic-phase chronic myeloid leukemia. Semin Hematol 2003; 40 (2 Suppl 2): 26–30.

    Article  PubMed  Google Scholar 

  11. Blanke C . Current management of GIST. Clin Adv Hematol Oncol 2004; 2: 280–283.

    PubMed  Google Scholar 

  12. Vuorinen K, Gao F, Oury TD, Kinnula VL, Myllarniemi M . Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia. Exp Lung Res 2007; 33: 357–373.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chaudhary NI, Roth GJ, Hilberg F, Muller-Quernheim J, Prasse A, Zissel G et al. Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis. Eur Respir J 2007; 29: 976–985.

    Article  CAS  PubMed  Google Scholar 

  14. Daniels CE, Wilkes MC, Edens M, Kottom TJ, Murphy SJ, Limper AH et al. Imatinib mesylate inhibits the profibrogenic activity of TGF-beta and prevents bleomycin-mediated lung fibrosis. J Clin Invest 2004; 114: 1308–1316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sandler C, Joutsiniemi S, Lindstedt KA, Juutilainen T, Kovanen PT, Eklund KK . Imatinib mesylate inhibits platelet derived growth factor stimulated proliferation of rheumatoid synovial fibroblasts. Biochem Biophys Res Commun 2006; 347: 31–35.

    Article  CAS  PubMed  Google Scholar 

  16. Soria A, Cario-Andre M, Lepreux S, Rezvani HR, Pasquet JM, Pain C et al. The effect of imatinib (Glivec) on scleroderma and normal dermal fibroblasts: a preclinical study. Dermatology 2008; 216: 109–117.

    Article  CAS  PubMed  Google Scholar 

  17. Rodnan GP, Lipinski E, Luksick J . Skin thickness and collagen content in progressive systemic sclerosis and localized scleroderma. Arthritis Rheum 1979; 22: 130–140.

    Article  CAS  PubMed  Google Scholar 

  18. Guardiola P, Runde V, Bacigalupo A, Ruutu T, Locatelli F, Boogaerts MA et al. Retrospective comparison of bone marrow and granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells for allogeneic stem cell transplantation using HLA identical sibling donors in myelodysplastic syndromes. Blood 2002; 99: 4370–4378.

    Article  CAS  PubMed  Google Scholar 

  19. Storek J, Gooley T, Siadak M, Bensinger WI, Maloney DG, Chauncey TR et al. Allogeneic peripheral blood stem cell transplantation may be associated with a high risk of chronic graft-versus-host disease. Blood 1997; 90: 4705–4709.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  21. George J, Roulot D, Koteliansky VE, Bissell DM . In vivo inhibition of rat stellate cell activation by soluble transforming growth factor beta type II receptor: a potential new therapy for hepatic fibrosis. Proc Natl Acad Sci USA 1999; 96: 12719–12724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Johnson RJ, Raines EW, Floege J, Yoshimura A, Pritzl P, Alpers C et al. Inhibition of mesangial cell proliferation and matrix expansion in glomerulonephritis in the rat by antibody to platelet-derived growth factor. J Exp Med 1992; 175: 1413–1416.

    Article  CAS  PubMed  Google Scholar 

  23. Santiago B, Gutierrez-Canas I, Dotor J, Palao G, Lasarte JJ, Ruiz J et al. Topical application of a peptide inhibitor of transforming growth factor-beta1 ameliorates bleomycin-induced skin fibrosis. J Invest Dermatol 2005; 125: 450–455.

    Article  CAS  PubMed  Google Scholar 

  24. Denton CP, Merkel PA, Furst DE, Khanna D, Emery P, Hsu VM et al. Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192. Arthritis Rheum 2007; 56: 323–333.

    Article  CAS  PubMed  Google Scholar 

  25. Distler JH, Jungel A, Huber LC, Schulze-Horsel U, Zwerina J, Gay RE et al. Imatinib mesylate reduces production of extracellular matrix and prevents development of experimental dermal fibrosis. Arthritis Rheum 2007; 56: 311–322.

    Article  CAS  PubMed  Google Scholar 

  26. Kiani A, Habermann I, Schake K, Neubauer A, Rogge L, Ehninger G . Normal intrinsic Th1/Th2 balance in patients with chronic phase chronic myeloid leukemia not treated with interferon-alpha or imatinib. Haematologica 2003; 88: 754–761.

    PubMed  Google Scholar 

  27. Leder C, Ortler S, Seggewiss R, Einsele H, Wiendl H . Modulation of T-effector function by imatinib at the level of cytokine secretion. Exp Hematol 2007; 35: 1266–1271.

    Article  CAS  PubMed  Google Scholar 

  28. Mohty M, Blaise D, Olive D, Gaugler B . Imatinib: the narrow line between immune tolerance and activation. Trends Mol Med 2005; 11: 397–402.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are especially grateful to those two patients who kindly agreed for publication of their photos in this article.

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Authors and Affiliations

  1. Service des Maladies du Sang, Lille, France

    L Magro, V Coiteux, B Bruno, J-P Jouet & I Yakoub-Agha

  2. Service de Dermatologie, Lille, France

    B Catteau, J-P Jouet & I Yakoub-Agha

  3. EA2686, CHRU, Lille, France

    J-P Jouet & I Yakoub-Agha

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  1. L Magro
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Correspondence to I Yakoub-Agha.

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Magro, L., Catteau, B., Coiteux, V. et al. Efficacy of imatinib mesylate in the treatment of refractory sclerodermatous chronic GVHD. Bone Marrow Transplant 42, 757–760 (2008). https://doi.org/10.1038/bmt.2008.252

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