Adjuvant high-dose interferon alfa-2b in patients with high-risk melanoma.

We performed an analysis of toxicity and survival in stage III melanoma patients receiving adjuvant interferon alfa-2b (IFN). This was a retrospective single-arm analysis of 40 patients with stage III melanoma who received (IFN) administered at maximum tolerated doses of 20 mU/m2/day intravenously (i.v.) for 1 month and 10 mU/m2 three times per week subcutaneously (s.c.) for 48 weeks. Toxicity in our series is comparable to that experienced in the Eastern Cooperative Oncology Group (ECOG) 1684 trial, except for higher rates of dose-limiting myelosuppression and hepatotoxicity. All 40 patients experienced constitutional symptoms, but only 14/40 (35%) experienced grade 3 to 4 symptoms. Of the 40 patients, 36 (90%) experienced neurologic symptoms, but only seven (17.5%) experienced grade 3 to 4 neurotoxicity. Two patients stopped treatment because of severe psychiatric symptoms; one patient attempted suicide, and a psychosis developed in another. Thirty-nine (97.5%) patients experienced myelosuppression; 31 (77.5%) developing grade 3 to 4 myelosuppression. Hepatotoxicity was evident in 39 (97.5%) patients, and 26 (65%) experienced grade 3 to 4 hepatotoxicity. Three patients (7.5%) experienced mild renal toxicity. At a median follow-up of 27 months from initiation of therapy, there have been 19 relapses (47.5% disease-free survival [DFS]) and 10 deaths (75% OS) resulting from progression of disease. The DFS compares with the treatment arm in ECOG 1684 at 27 months, but overall survival is higher in our series of patients at the same time point. In a single program setting, IFN can be administered with similar side effects and outcome profiles seen in multi-institutional studies. Modifications in the induction regimen resulted in notably higher hematologic and hepatic toxicities but did not preclude administering further therapy and did not result in increased attrition rate among patients: only nine patients (22.5%) had their treatment stopped as a result of IFN-related toxicity. In comparison, 26% of patients had to have their treatment discontinued because of toxicity in ECOG 1684.

Epstein-Barr virus infection in renal transplant recipients. Effects of antithymocyte globulin and interferon.

We studied Epstein-Barr (EB) virus excretion and antibody in 41 renal transplant recipients enrolled in a placebo-controlled trial of human leukocyte interferon. Half the patients were also treated with antithymocyte globulin. Epstein-Barr virus excretion occurred more often in recipients of cadaver kidneys (P = 0.03) and those receiving antithymocyte globulin (P = 0.04) and less often in patients given interferon (P = 0.08). Antibody to viral capsid antigen increased fourfold or more in 12 of 22 patients treated with antithymocyte globulin and in none of the non-antithymocyte globulin-treated group (P = 0.0002). Antibody to the restricted component of early antigen rose fourfold or more in eight patients and appeared related to the occurrence of syndromes similar to those attributed to cytomegalovirus in transplant recipients. We conclude that increasing immunosuppression augments the rate of EB virus reactivation and that EB virus may be an important pathogen in heretofore ill-defined syndromes.

Impact of blood transfusion on renal transplantation.

The relationship between transfusion of different preparations of blood, sensitization to HLA antigens and survival of subsequent kidney transplants was investigated in 90 consecutive recipients. HLA lymphocytotoxins in transplant candidates precluded or greatly delayed receipt of an allograft (p less than 0.0005). Furthermore, only 17% of such sensitized recipients had functioning grafts one year after transplantation compared to 57% survival for nonsensitized recipients (p less than .02). A small number of nonsensitized patients who were never transfused had surprisingly poor one year graft survival (25%). If frozen blood is used for transfusion rather than whole/packed RBC, the incidence of patient sensitization can be markedly reduced without subsequent compromise in transplant survival (51%). It is concluded that as a consequence of avoiding HLA sensitization by transfusion of frozen blood (processed by agglomeration), the period of hemodialysis required for potential graft recipients will be shortened and an increased proportion of potential recipients will be successfully treated by transplantation.

Delayed perforation of the innominate vein during hyperalimentation.

Mechanical complications of central vein catheterization for hyperalimentation typically become manifest shortly after insertion. We present a case report describing a delayed innominate vein perforation by a central venous catheter. Use of the adult internal jugular vein for central venous catheterization should be limited to situations in which a subclavian vein is unavailable. Ongoing watchfulness and a vigorous diagnostic and therapeutic approach to such complications are mandatory in the treatment of patients receiving total parenteral nutrition.