Liver and kidney transplantation in children receiving cyclosporin A and steroids

Abstract

The new immunosuppressive agent, cyclosporin A, was used with low doses of steroids to treat eight patients undergoing hepatic transplantation and three patients undergoing cadaveric renal transplantation. Seven of the eight liver recipients are well, including one who was given two livers. The three kidney recipients, who had developed cytotoxic antibodies after previously rejecting grafts with conventional immunosuppressive therapy, have had good results despite conditions which usually preclude attempts at transplantation. The ability to control rejection effectively and safely without chronic high-dose steroid therapy may make the described therapeutic regimen valuable for pediatric recipients of whole organs.Cadaveric organ transplantation in infants and children has been an unreliable and morbidity-laden undertaking. The ability to control rejection has been unpredictable with conventional immunosuppressive therapy including azathioprine and prednisone with or without anti-lymphocyte globulin. Even with "success" the frequent need for high-dose steroid therapy has all too often degraded the quality of post-transplantation life.We report here an alternative method of immunosuppression with cyclosporin A and low doses of steroids that has been used in eight liver and three cadaveric kidney recipients who have been followed for 3½ months to 1⅓ years. Although the experience is small and the follow-up periods short, the results have made us believe that transplantation of a variety of organs will become a practical reality in larger numbers of pediatric health care centers. METHODS Case materialLiver recipients-The eight patients were 2⅙ to 16 years of age (Table I). Four had biliary atresia; of these, three had had one or more previous attempts at porticoenterostomy (Kasai procedure), and the earlier operations made transplantation difficult. Other diagnoses are shown in Table I.Donor selection was random in respect to the HLA A, B and D loci. Matches of the four antigens of the A and B loci averaged 1.0 ± 0.7 (SD), range 0 to 2. Two DR matches were present in one case, one match existed in two cases, and no matches were present in the other six donor-recipient combinations.

Antilymphoid antibody preconditioning and tacrolimus monotherapy for pediatric kidney transplantation

“…Reliable prevention of acute rejection resulted, as well as reduction in the use of steroids. [8][9][10][11][12][13] However, the drastic weaning from immunosuppression accomplished in the early cases was almost never accomplished. Efforts to improve the complex protocols were frustrated for many years because the mechanisms of organ engraftment, and the effect of immunosuppression on these mechanisms, were unknown.…”

Linear Growth Following Pediatric Liver Transplantation

“…Cyclosporine and prednisone 2,3 were administered in doses that were tapered as quickly as was consistent with avoidance of rejection, 4,5 Patients received 2.5 to 5 mg of prednisone as a single daily dose and an average dosage of 9.4 mg/kg/d of cyclosporine (range, 4.6 to 20 mg/kg/d) divided twice daily. Whole blood cyclosporine levels were measured by highperformance liquid chromatography 6 with maintenance of trough levels between 100 to 350 ng/mL (83 to 291 nmol/L).…”

“…Survival of both the patient and graft, as well as quality of life, have been improved with transplantation of kidneys and livers in adults 2 ; similar improvement has been predicted for children. 3 Detailed growth studies with the use of cyclosporine and prednisone for immunosuppression have been limited to kidney transplantation recipients. The reports of Conley et al 15 and Klare et al 16 have been optimistic, whereas Ellis et al 17 described poor or absent growth in seven of their eight kidney recipients.…”

Early tolerance in pediatric liver allograft recipients

“…The fact that immunosuppression can be reduced 1,11 or stopped 8 after transplantation is best exemplified in pediatric patients. In them immunosuppression is automatically down-regulated because no increase is made to compensate for growth.…”