Pathogenesis and recent therapeutic approaches to graft-versus-host disease

Effective prophylaxis of acute GVHD should bring about improved patient survival by decreasing severe infections during the first 3 months after transplantation and reducing the incidence of chronic GVHD while not compromising the quality of hematopoietic engraftment or increasing the incidence of leukemic relapse by impairing the graft-versus-leukemia effect. None of the current approaches to prevention of GVHD succeed at meeting these expectations, although postgrafting immunosuppressive therapy comes closest to the ideal. The technique of T cell depletion has been very effective in reducing the incidence of GVHD, but conditioning programs must be developed that will be more successful at eliminating host immune and malignant cells. It is doubtful that this will be achieved with systemic chemotherapy and total body irradiation. Innovative approaches such as the use of monoclonal antibodies, either alone or linked to short-lived radioactive isotopes with short linear energy transfer, promise to result in less toxic but more efficient programs, not only providing better eradication of malignant disease but also ameliorating the problem of graft failure. It is conceivable, however, that it will never be possible to kill all leukemic cells with chemoradiotherapy of any form, and the graft-versus-leukemia effect may be essential. Perhaps in the future it will be possible to distinguish lymphocytes causing the graft-versus-leukemia effect from those causing GVHD, isolate them, and use them in attempts at therapy. In the meantime, postgrafting immunosuppressive drugs are used most frequently to prevent and treat GVHD, and steadily improving survival statistics can be expected.