Use of OKT3 with ciclosporin and steroids for reversal of acute kidney and liver allograft rejection

OKT3 monoclonal antibody therapy was added to preexisting baseline immunosuppressive treatment with ciclosporin and steroids to treat rejection in 52 recipients of cadaveric livers and 10 recipients of cadaveric kidneys. Rejection was controlled in 75% of patients treated, often after high-dose steroid therapy had failed. Rejection recurred during the 17-month follow-up period, after completion of OKT3, in only 25% of the patients who had responded. The safety and effectiveness of this monoclonal therapy, added to ciclosporin and steroids, has been established in this study

EPSTEIN-BARR-VIRUS ASSOCIATED SYNDROMES IN IMMUNOSUPPRESSED LIVER-TRANSPLANT RECIPIENTS - CLINICAL PROFILE AND RECOGNITION ON ROUTINE ALLOGRAFT BIOPSY

The clinical profile and histopathologic changes in needle biopsies of the liver were studied in 10 cases of acute Epstein-Barr virus infection occurring in liver transplant recipients. The systemic viral syndrome in four cases resembled that seen in infectious mononucleosis, whereas in six others it was characterized by atypical signs and symptoms in the form of jaw pain, arthralgias, joint space effusions, diarrhea, encephalitis, pneumonitis, mediastinal lymphodenopathy, and ascites. Laboratory investigation showed marked elevations in hepatocellular enzymes and circulating atypical lymphocytes in the peripheral blood. Pancytopenia was noted in eight cases. A range of histopathologic changes was noted in the allografts ranging from alterations typically observed in infectious mononucleosis to a distinctive constellation characterized by (a) mixed mononuclear portal and sinusoidal infiltrates containing atypical large noncleaved cells and immunoblasts; (b) associated lobular activity indicative of a hepatitic process, and (c) relatively mild duct damage not in proportion to the severity of the inflammatory infiltrates. The patients responded to reduced immunosuppression, but recurrent viral syndromes occurred in four instances and one patient died of systemic lymphoproliferative disease

Prevention of transplant rejection can tolerance be achieved with immunosuppressive treatment?

Successful solid organ transplantation is generally attributed to the increasingly precise ability of drugs to control rejection. However, it was recently shown that a few donor haematolymphoid cells can survive for decades in recipients of successful organ allografts, a phenomenon called microchimaerism. The association for decades of haematolymphoid chimaerism with allograft tolerance in experimental transplantation suggests that immunosuppressive drugs merely create a milieu that enables an allograft and its complement of passenger leucocytes to prime the recipient for graft acceptance. Exploitation of this concept requires a fundamental shift in the classical view of passenger leucocytes only as initiators of rejection. Microchimaerism has taught us that solid organ transplantation involves the transfep-öTEwo3öTK}r organ systems to the recipient: the allograft parenchyma an-4oHg-4oonor'-4y&eWtolymphoid system in the form of donor stem cells contajfletwit|4Q(Xj pas-4MTger leucocyte compartment. Each has the potential to integral witty-4-4orrespSnping recipient system and carry out normal physiologi|:a£futy-4ijj£jvwlta5irnmunological self definition. Resistance to initial integralen r-4WMjure £als requires some form of immunosuppression, but mainterçad-4 of donor-4Rjraiine system function will depend on renewable supply of cells, v-4Jrf-4Siyi-4jj-4fvided by engrafted progenitors. Successful clinical application willctepcrrtTon the development of low morbidity methods to enhance engraftment of donor haemopoietic stem cells. Adis international Limited All rights reserved