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Steroid-refractory acute graft-versus-host disease (GVHD)


Authors: J. Mayer 1;  P. Cetkovský 2;  M. Krejčí 1
Authors‘ workplace: Interní hematoonkologická klinika FN Brno 1;  Ústav hematologie a krevní transfúze Praha za organizaci Česká leukemická skupina – pro život, The CzEch Leukemia Study Group – for Life, CELL 2
Published in: Transfuze Hematol. dnes,13, 2007, No. 4, p. 192-199.
Category: Comprehensive Reports, Original Papers, Case Reports

Overview

Graft-versus-host disease (GVHD) represents one of the main complications after performance of allogeneic hematopoietic stem cell transplantation. T-lymphocytes from the graft are responsible for GVHD. Acute GVHD (aGVHD) develops within the day +100 after allogeneic transplantation, aGVHD impacts usually skin, liver or mucosa of gastrointestinal tract. The clinical manifestation of aGVHD is various and it represents mostly combination of impairment of more organs. Corticosteroids in dose 2 mg/kg are the standard first-line treatment, however, they are effective in 50% of patients only. Corticosteroid-resistant aGVHD is difficult to manage, and it is associated with high morbidity and mortality. Definition of steroid-resistant aGVHD varied, it is usually no response to corticosteroids after 3-14 days of treatment. The article summaries treatment possibilities in steroid-refractory aGVHD, with inclusion of the results of clinical trials published on this topic. Treatment of steroid-refractory aGVHD can be divided into four groups. The non-specific elimination of T-lymfocytes is used in the first group, representative agents are antithymocyte globulin, antilymphocyte globulin, alemtuzumab, denileukin diftitox and monoclonal antibodies anti-CD2, anti-CD3, anti-CD147. The drugs influencing cytokines or their receptors are in the second group, such as daclizumab (antibody against receptor for interleukin-2), infliximab and etanercept (inhibitors of tumor necrosis factor). The third group includes cytostatics and immunosuppressive agents, such as cyclophosphamide, methotrexate, mycophenolate mofetil, pentostatin, sirolimus. The cell therapy and other possibilities, such as treatment with rituximab and extracorporeal photopheresis are discussed in the fourth group. All treatment approaches for steroid-refractory GVHD are only partially efficient. Steroid-refractory aGVHD remains a serious therapeutic problem.

Key words:
acute GVHD, steroid-refractory, treatment


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