The concept of GvHD-suppression by in vitro treatment with antisera.

Abstract

Progress in chemotherapy during the past decade resulted in considerable improvement in treatment of acute leukemias. Once the first relapse occurs, however, prognosis for prolonged survival is poor. The patient finally reaches an end stage of the disease which no longer responds to chemotherapy. In these cases the application of bone marrow transplantation opens up a second chance for a long lasting remission. Leukemic cells were eradicated by a short intensive course of chemotherapy and total body irradiation followed by a marrow infusion from a suitable donor to rescue the patient from the otherwise lethal marrow cell damage. One major obstacle to the successful application of allogeneic bone marrow transplantation is the occurence of immunologic complications when donor and recipient are not monozygous twins and express differences in their histocompatibility properties. The bidirectional immunologic barrier may cause a rejection of the marrow graft or a graft-ver-sus-host reaction induced by immunocompetent T-lymphocytes in the donor marrow. Whereas graft rejection is supressed with increasing success by the intensive conditioning treatment of the leukemic patients, graftversus-host disease (GvHD) is still a frequent problem of clinical bone marrow transplantation (Thomas et al. 1977). The disease is presumably attributable to a cytopathogenic reaction of immunocompetent donor T lymphocytes of the graft on host target tissues (Slavin and Santos 1973). Even after transplantation of HLA-identical and MLC-negative marrow grafts the occurence of GvHD cannot be excluded due to genetic differences not detected by present histocompatibility typing techniques.