Avascular necrosis of bone after cardiac transplantation. Prevalence and relationship to administration and dosage of steroids.

We studied the relationship of the administration and dosage of steroids to the development of avascular necrosis of bone in 168 patients who had had a heart transplantation (156 patients) or a heart and lung transplantation (twelve patients). One hundred and forty-one of the patients were male and twenty-seven were female. The average age was forty-five years (range, seven to sixty-six years). The average duration of follow-up was forty months (range, twelve to eighty months). Avascular necrosis developed in five patients (3 per cent). The femoral head was involved in three patients (bilaterally in two and unilaterally in one), the medial femoral condyle was involved bilaterally in one, and several sites were involved in the fifth patient. The avascular necrosis was diagnosed an average of five months (range, two to eleven months) after the transplantation. In order to evaluate the influence of the dosage of the steroids on the development of avascular necrosis of bone, the doses of prednisone and Solu-Medrol (methylprednisolone) at one week, one month, six months, and one year after the transplantation were calculated for each patient. There was no association between the cumulative dose of prednisone and the development of avascular necrosis. There was, however, a strong statistical association (p = 0.005), as determined with pooled two-tailed variance analysis, between the cumulative dose of Solu-Medrol administered in the first month after the transplantation and the development of avascular necrosis.

Avascular necrosis superimposed on Legg-Calvé-Perthes disease in a cardiac transplant patient.

The pathogenesis of both Legg-Calvé-Perthes disease (LCPD) and avascular necrosis (AVN) remains controversial. Evidence suggests, however, that both conditions are produced by vascular compromise in the femoral head. A patient with a previous history of LCPD at age eight subsequently developed AVN at age 46 after having a cardiac transplant for ischemic cardiomyopathy. A review of the past ten years' literature disclosed no reports of similar cases.

Rabbit antithymocyte globulin. A 10-year experience in cardiac transplantation.

Rabbit antithymocyte globulin, a "custom-made" pan-anti-T-cell antibody produced in rabbits, is currently being evaluated in the United States and may, within several years, become approved by the Food and Drug Administration. Because we have used this agent for induction of immunosuppression for 10 years in cardiac recipients and because the results appear to be more favorable than those obtained with other agents (horse antithymocyte globulin, antilymphocyte globulin, OKT3), we have reviewed our experience. For the purpose of analysis, all non-bridge-to-transplant cardiac recipients have been divided into three groups on the basis of immunosuppression protocol: group I (March 1979 to January 1983), 28 patients treated with rabbit antithymocyte globulin, steroids, and azathioprine; group II (January 1983 to March 1985), 29 patients treated with rabbit antithymocyte globulin, cyclosporine, and steroids; and group III (March 1985 to January 1989), 98 patients treated with rabbit antithymocyte globulin, cyclosporine, steroids, and azathioprine. Actuarial data showed advantage for group III in survival rate (1 year 94%, 2 years 91%, 3 years 88%), freedom from rejection (30% free at 1 year), freedom from infection (50% free at 1 year), freedom from death from rejection (99% free at 1 year), and freedom from death from infection (97% freedom at 1 year). Actuarial survival rates and freedom from death from rejection and infection are comparable for any of our groups with contemporary published data. In the past 3 years, we have had no death from acute rejection or from posttransplant infection. Time-related rates of infection by etiologic agents have shown a significant reduction in early bacterial, viral, and nocardial infections between groups I and III. With rabbit antithymocyte globulin 200 mg intramuscularly every day for 3 days, our current protocol, T-cells are significantly reduced and local and systemic toxicity is almost unnoticeable. A progressively increasing cyclosporine dose along with rapid tapering steroid and maintenance azathioprine immunosuppressive induction appears to be the therapy of choice in cardiac transplantation.