Graft-versus-host disease in allogeneic bone marrow transplantation: the role of monoclonal antibodies in prevention and treatment.
Reconstitution of an individual's haemopoietic stem cells by bone marrow transplantation (BMT) is the recommended treatment for a number of haematological conditions, both malignant and non-malignant. Despite evolution in BMT technology over the past forty years, graft-versus-host disease (GvHD) remains a major, potentially lethal complication. GvHD normally affects the skin, liver and gastrointestinal tract, resulting in a high rate of morbidity. The standard prophylaxis for GvHD is a combination of methotrexate and cyclosporin A, but this is only partially effective. Acute GvHD is difficult to treat and many patients are resistant to steroid therapy. Alternative methods of prevention and treatment are now being sought, and include monoclonal antibodies (MAbs) which target T cells and cytokines. T-cell depletion of donor marrow using rat MAbs reduces the incidence of GvHD but can increase the chances of leukaemic relapse. Mouse MAbs also have been used but some produce severe side-effects. The most successful MAbs are those linked to toxins, and these immunotoxins (IT) have proved very effective in reversing steroid-resistant acute GvHD. MAb therapies are becoming increasingly important in the treatment and prevention of GvHD, and could replace steroids as the main treatment option in some situations. It is predicted that, ultimately, peripheral blood stem-cell transplantation will replace the use of BMT; however, this alternative stem-cell source will not remove the GvHD risks associated with allogeneic stem-cell transplantation. Therefore, reducing the risks will remain a major challenge in the successful allogeneic transplantation of haemopoeitic stem cells for the foreseeable future.
Centre for Applied Microbiology and Research, Salisbury, UK.
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Hiscott
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McLellan
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D006086:Graft vs Host Disease / Q000209:etiology / Q000628:therapy*; D006801:Humans
D000911:Antibodies, Monoclonal