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Treatment of steroid-resistant acute graft-versus-host diseas

Piotr Rzepecki, Krzysztof Gawroński, Beata Młot, Sylwia Oborska, Wojciech Pielichowski, Anna Waśko-Grabowska

Affiliacja i adres do korespondencji
CURR. GYNECOL. ONCOL. 2011, 9 (4), p. 253-263
Streszczenie

Use of allogeneic hematopoietic stem cell transplantation is increasing continuously as a consequence of continuing progress of medical techniques, allowing implementation of this procedure even in patients where previously it was considered contraindicated. It is successfully used in the treatment of both several hematologic malignancies and other conditions. Still, a major concern remains the development of graft-versus-host disease (GvHD) as a complication of this kind of therapy. Treatment of choice in acute forms of stage II-IV GvHD are steroids (prednisolone, 1-2 mg/kg/d) combined with calcineurin inhibitors (cyclosporine A or tacrolimus). Steroid-resistant patients constitute a considerable therapeutic challenge, as they require enhanced immunosuppression. Standard management of these patients depends on experiences of particular center and usually an individual therapeutic strategy is warranted. No controlled clinical trials are available, documenting a favorable effect on survival of a particular salvage procedure in the setting of a steroid-resistant GvHD. In this situation, the following agents may be used: mycophenolate mofetil, methotrexate, pentostatin, mTOR inhibitors, anti-TNF-α and anti-IL-2 antibodies as well as mono- and polyclonal anti-T-lymphocyte antibodies. Non-pharmacological options include the use of extracorporeal photopheresis and infusion of allogeneic mesenchymal stem cells. In order to improve its effectiveness, salvage therapy should be instituted as quickly as possible, at best during the first 2 weeks after diagnosis of GvHD. Nevertheless, overall effectiveness and toxicity of most therapeutic modalities are far from satisfactory. Current research focuses on regulatory T-lymphocytes and small molecules affecting signal transmission between antigen-presenting cells and effector cells.

Słowa kluczowe
acute graft-versus-host disease, salvage treatment, allogeneic hematopoietic stem cell transplantation, mesenchymal stem cells, extracorporeal photopheresis