Intravenous immunoglobulin reduces anti-HLA alloreactivity and shortens waiting time to cardiac transplantation in highly sensitized left ventricularassist device recipients

Background-Recipients of left ventricular assist devices (LVADs) develop pr ominent B-cell hyperreactivity. We investigated the influence of anti-HLA a ntibodies on waiting time to cardiac transplantation in LVAD recipients and compared the effects of 2 immunomodulatory regimens on anti-HLA serum reac tivity. Methods and Results-Fifty-five previously nonsensitized LVAD recipients of a TCI device implanted between 1990 and 1996 were studied. Patients with an ti-HLA antibodies received monthly courses of either intravenous immunoglob ulin (IVIg) or plasmapheresis, in conjunction with cyclophosphamide. The ef fects of these regimens on anti-HLA alloreactivity and waiting time to tran splantation were then determined by Kaplan-Meier log-rank statistics, nonpa rametric Wilcoxon rank-sum test, and Student's t test. Prolongation in tran splant waiting time was related to serum Ige anti-HLA class I alloreactivit y. Infusion of IVIg (2 g/kg) caused a mean reduction of 33% in anti-HLA cla ss I alloreactivity within 1 week. Waiting time to transplantation was sign ificantly reduced by IVIg therapy and subsequently approximated that in non sensitized patients. Side effects of IVIg (2 g/kg) were minimal and related primarily to immune complex disease. Although plasmapheresis caused a simi lar reduction in alloreactivity to IVIg, this effect was achieved after lon ger treatment. Moreover, plasmapheresis was associated with an unacceptably high frequency of infectious complications. In patients resistant to low-d ose (2 g/kg) IVIg therapy, high-dose (3 g/kg) IVIg was effective in reducin g alloreactivity but was associated with a high incidence of reversible ren al insufficiency. Conclusions-These results indicate that IVIg is an effective and safe modal ity for sensitized recipients awaiting cardiac transplantation, reducing se rum anti-HLA alloreactivity and shortening the duration to transplantation. The therapeutic and safety profile of IVIg would appear to be superior to plasmapheresis.