Intravenous Immunoglobulin Therapy in Highly Sensitized Cardiac Allograft Recipients Facilitates Transplantation Across Donor Specific IGG Positive Cross Matches

Sensitized patients awaiting cardiac transplantation are subject to prolonged waiting times as a result of repeated positive cross-matches, and are at increased risk of humoral rejection post-transplant. We review our experience with 35 highly sensitized patients awaiting a cardiac allograft who were treated with IVIg therapy at monthly doses of 2-3 g/kg (31 had LVADs, 2 retransplants, mean recipient age 44+16.5 years). All patients also received cyclophosphamide in a single infusion dose of 0.5 to 1.0 g/m2 monthly pre-transplant and for three to four months post-transplant. The effect of this regimen on anti-HLA IgG alloreactivity, humoral rejection, and survival were determined. Of 71 courses of IVIg therapy pre-transplant, 47 (66%) resulted in a reduction in anti-HLA alloreactivity. Treatment with IVIg resulted in 39% mean reduction in anti-HLA class I alloreactivity, with 28 of 35 patients having negative donor-specific cross-matches prior to transplantation. Of these, only 1 developed humoral rejection post-transplant. Of 7 patients transplanted across a positive prospective IgG donor-specific cross-match, 3 developed humoral rejection within 1-4 weeks post-transplant. In all but one case humoral rejection was adequately managed with either repeat courses of IVIg or intermittent plasmapheresis. By Kaplan-Meier analysis, actuarial survival for sensitized patients treated with IVIg and IV cyclophosphamide at 1 and 3 years following transplantation was 93% and 93%, respectively. In contrast, post-transplant survival in non-sensitized LVAD patients treated with conventional immunosuppression was 79% and 76 % at 1 and 3 years following transplantation. We conclude that a treatment regimen consisting of IVIg and IV cyclophosphamide therapy reduces alloreactivity in sensitized patients awaiting cardiac transplantation, increases the likelihood of obtaining negative cross-matches, and facilitates successful transplantation even across a positive prospective donor-specific cross match. Moreover, this regimen appears to be associated with better 1- and 3-year survival in patients at high risk for sensitization than conventional immunosuppressive regimens.