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Etanercept in graft-versus-host disease

Bone Marrow Transplantation volume 26, page 929 (2000)Cite this article

Graft-versus-host disease (GVHD) represents a serious complication of allogeneic BMT and remains one of the most difficult challenges for clinicians. Recent advances in the understanding of the cytokine network as well of direct mediators of cellular cytoxicity have led to improved knowledge of this complex disease process.1 A critical role for TNF-α in the pathophysiology of acute GVHD was first suggested almost 10 years ago2 and was recently confirmed, especially in cases with the pathological features of inflammatory bowel disease.3 Moreover, the role of a TNF inhibitor was studied in irradiated mice in which the administration of an adenoviral vector encoding a TNF inhibitor protein improved intestinal symptoms.4 Etanercept is a genetically engineered fusion protein consisting of two identical chains of the recombinant extracellular human TNF-receptor p75 monomer fused with the Fc domain of human IgG1 which binds TNF and lymphotoxin-a and inhibits their activity.5 It’s safety and efficacy was demonstrated in children with polyarticular juvenile rheumatoid arthritis.6 We report a case of GVHD which developed after bone marrow transplantation (BMT) and which improved after treatment with etanercept.

An 11-year-old girl suffering from myeloid leukemia in chronic phase underwent a BMT from a matched unrelated donor. The conditioning regimen was busulphan, thiotepa and cyclophosphamide plus ALG, while methotrexate and cyclosporine were used as GVHD prophylaxis. On the 40th day after BMT she developed a severe intestinal GVHD which was treated with methylprednisolone, somatostatine, loperamide and total parenteral nutrition. Gastrointestinal endoscopy showed diffuse ulcerations, mucosal sloughs and hemorrhagic areas involving the stomach, duodenum, rectum and colon, with histological findings characterized by marked lymphocytic infiltration, crypt-cell necrosis and dropout. The symptoms became chronic and every attempt of oral feeding caused deterioration. The number of platelets was always less than 50 × 109/l and the patient developed a restrictive pulmonary disease. Moreover, a recurrent cytomegalovirus antigenemia hindered the possibility of more intensive immunosuppressive treatment. Thus, we started therapy with etanercept at a dose of 0.4 mg/kg subcutaneously twice a week. The gastrointestinal symptoms slowly disappeared and after 2 months she was able to feed normally. The gastrointestinal biopsy showed only a soft intestinal oedema with a moderate lymphocytic infiltration. Meanwhile, the pulmonary disease also improved (evidenced by spirometry with a total lung capacity changed from 1 to 2.4 liters) and the level of platelets rose above 100 × 109/l. At the 5th month the treatment was withdrawn. The gastrointestinal symptoms reappeared within 3 weeks and the level of platelets dropped to less than 50 × 109/l. We started the treatment again at the same dosage and a new complete remission was achieved. After 12 months of treatment the patient is in good condition (Karnofski score >90) and does not need further immunosuppressive treatment. No adverse events were noticed.

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References

  1. Vogelsang GB, Hess AD . Graft-versus-host-disease: new directions for a persistent problem Blood 1994 84: 2061–2067

    CAS  PubMed  Google Scholar 

  2. Piguet PF, Grau GE, Allet B, Vassalli PJ . Tumor necrosis factor/cachetin is an effector of skin and gut lesion of the acute phase of graft-versus-host-disease J Exp Med 1987 166: 1280–1289

    Article  CAS  Google Scholar 

  3. Hattori K, Hirano T, Miyajima H et al. Differential effects of anti-Fas ligand and anti-tumor necrosis factor alpha antibodies on acute graft-versus-host disease pathologies Blood 1998 91: 4051–4055

    CAS  PubMed  Google Scholar 

  4. Brown GR, Lindberg G, Meddings J et al. Tumor necrosis factor inhibitor ameliorates murine intestinal graft-versus-host disease Gastroenterology 1999 116: 593–601

    Article  CAS  Google Scholar 

  5. Mohler KM, Torrance DS, Smith CA et al . Soluble tumor necrosis factor receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonist J Immunol 1993 151: 1548–1561

    CAS  PubMed  Google Scholar 

  6. Lovell DJ, Giannini EH, Reiff A et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis New Engl J Med 2000 342: 763–769

    Article  CAS  Google Scholar 

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  1. Bone Marrow Unit, Institute of Maternal and Child Health, Via dell’Istria 65/1, Trieste, Italy

    M Andolina, M Rabusin, N Maximova & G Di Leo

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  1. M Andolina
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  2. M Rabusin
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  3. N Maximova
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  4. G Di Leo
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Andolina, M., Rabusin, M., Maximova, N. et al. Etanercept in graft-versus-host disease. Bone Marrow Transplant 26, 929 (2000). https://doi.org/10.1038/sj.bmt.1702638

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