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PURPOSE: To assess the efficacy of acyclovir and intravenous immune globulin (IVIG) for cytomegalovirus (CMV) prophylaxis in high-risk recipients of solid organ transplants. PATIENTS AND METHODS: We randomized 21 CMV-seronegative organ transplant recipients with seropositive donors (D+R-) to receive oral acyclovir, 800 mg four times daily, or, in addition to acyclovir, IVIG, 300 mg/kg, every 2 weeks for six doses. Patients were followed closely for the development of CMV infection and disease. RESULTS: All but one prophylactically treated patient (95%) developed CMV infection. Fifteen of 21 patients (71%) who received prophylaxis fulfilled criteria for CMV disease. Disease onset was delayed in those who received IVIG, but this did not reach statistical significance. Ganciclovir was used for treatment in 15 of the 21 patients (71%). CONCLUSIONS: Acyclovir, with or without IVIG, did not prevent primary CMV infection or disease in D+R- solid organ transplant recipients at our institution. Moreover, most patients were treated with ganciclovir despite the use of prophylaxis. Given the ready availability of ganciclovir to treat CMV disease, we recommend a reappraisal of the role of CMV prophylaxis by these means in the solid organ transplant population.

One approach to the treatment of type I diabetes (insulin-dependent diabetes mellitus) involves allografts (transplants from donors) of beta-cells from the pancreas. In type I diabetes, the beta-cells are destroyed, and since they normally produce insulin, this leads to uncontrolled high blood sugars. Transplantation of beta-cells has had only limited success to date, in part because of difficulty obtaining sufficient numbers of beta-cells for transplant in order to maintain normal blood sugar levels in the recipient patient. This report documents the first successful beta-cell allograft that was able to entirely eliminate the need for insulin injections. The recipient was a 36-year-old woman who had suffered from type I diabetes for 27 years, and who had received an unsuccessful pancreas transplant (whole organ) and a successful kidney transplant. Beta-cells (contained in the islets of Langerhans) were isolated from two cadaver donors (800,000 islets total), and were injected into an abdominal vein under local anesthesia. The patient was maintained on insulin therapy and immunosuppressive treatment (to prevent rejection of the allograft) for 10 days following surgery, at which time the insulin was discontinued. Blood sugar levels were maintained within normal limits, and responses to metabolic challenges were normal, indicating that the beta-cells were fully functional. Several months after surgery, when the patient went through significant personal stresses including the death of a family member, blood sugar levels rose above acceptable values, and insulin therapy was reinstituted. Inasmuch as the insulin therapy is still being administered (and beta-cell function has not yet been redetermined), it is not known whether this failure reflects an acute stress response, or a rejection of the allograft. (Consumer Summary produced by Reliance Medical Information, Inc.)

With the first demonstration of insulin independence following intraportal islet transplantation into a patient with type 1 diabetes, a new era of clinical islet transplantation will begin. This report provides our initial experience of clinical islet transplantion with a total of nine consecutive portal vein islet trasplants in seven diabetic recipients. The first three transplants were done in nonrenal failure diabetics (NRFI) using 6319±2173 islets/kg body weight with islets processed from single pancreas and cultured for 7 days at 24±C. Prednisone, azathioprine, and cyclosporine were initiated prior to transplant. While all three recipients demonstrated C-peptide function posttransplant, all three rejected their grafts at 2 weeks. Five days of OKT3 treatment failed to recover more than 10 of their rejecting islet grafts. The studies were then shifted to established kidney transplant recipients (EKI) maintaining their basal immunosuppression while adding 7 days of Minnesota antilymphoblast globulin (MALG) to the recipient using islets from single donor pancreas that had been cultured for 7 days at 24±C. There were an average of 6161 ± 911 islets transplanted intraportally into three EKI recipients. All three had C-peptide response from the transplant, but none achieved insulin independence. While the first patient rejected his graft at 2 weeks, two recipients demonstrated long-term islet function up to 10 months posttransplant. Sustacal challenge testing demonstrated C-peptide responsiveness, but in a delayed pattern suggesting insufficient islet mass had been transplanted. The next three kidney transplant recipients received islets from more than one donor pancreas averaging 13,916 ± 556 islets/kg body weight. The first of these was the first to achieve insulin independence from 10 to day 25 posttransplant when she appeared to have a rejection episode. The second and third recipients were retransplanted with islets from multiple donorshaving achieved partial islet function from single pancreas donor. The first patient on triple immunosuppression is demonstrating long-term partial function at 184 days but is not insulin independent. The third patient on prednisone and azathioprine received one half his islets after 7-day culture and the other half after 7-day culture combined with cryopreservation. He is continuing to demonstrate insulin independence for 154 days post-transplant with a glycated hemoglobin value of 5.6. Sustacal challenge data demonstrate a total stimulated C-peptide response of 155 ρmol/ml at 4 months posttransplant compared with 148±12 ρmol/ml for normal controls (NC) and 425 ρmol/ml for nondiabetic, established kidney transplant recipients on triple immunosuppression. These results demonstrate the feasibility of achieving insulin independence in type 1 patients after islet transplantation and justify continuing these studies to document how many recipients of islet transplantation can achieve insulin independence for what duration posttransplant.