Renal dysfunction associated with the administration of high-dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal carcinoma.

PURPOSE: To describe the incidence and management of renal dysfunction associated with the use of high-dose interleukin-2 (IL-2) (as is currently approved) in the treatment of cancer patients. PATIENTS AND METHODS: One hundred ninety-nine consecutive patients with metastatic renal carcinoma or melanoma were treated with intravenous bolus infusions of IL-2 alone (720,000 IU/kg) every 8 hours. RESULTS: Patients received 310 courses (589 cycles) of therapy and most experienced oliguria, hypotension, and weight gain; 13% of cycles were discontinued due to increased serum creatinine levels. Creatinine values (mean pretherapy, 1.2 mg/dL) increased during therapy and peaked (mean, 2.7 mg/dL) approximately 1 day after discontinuation of the second cycle of IL-2. Off therapy, toxicities reversed promptly and creatinine values returned to baseline. Higher peak creatinine values occurred in patients with renal carcinoma (v melanoma), older patients, males (v females), and those who had undergone prior nephrectomy. These same patient subsets received fewer doses of IL-2, but clinical responses were not associated with creatinine values or number of IL-2 doses administered. Urinalyses showed the appearance of protein, bilirubin, RBCs, WBCs, and granular casts during therapy, which cleared completely on follow-up evaluation. CONCLUSION: High-dose IL-2 can be safely administered to cancer patients. The associated renal dysfunction is transient and without evidence of intrinsic long-term renal damage. Practical guidelines for patient management have been identified.

Experience with schistosomiasis in renal transplantation.

Schistosomiasis involving the urinary tract has only occasionally been reported in North American literature and rarely from American hospital experience. Chronic infection may result in numerous abnormalities of the urinary tract which may interfere with the function of a transplanted kidney. Our institution has performed a number of renal transplants in patients who are from countries where schistosomiasis is endemic. Six patients in our group had evidence of schistosomal disease during their pretransplant evaluation and were appropriately treated. None of these patients had postoperative complications attributable to the schistosomal disease. We recommend that all patients who are from areas where urinary schistosomiasis is endemic undergo a cystoscopic examination and bladder biopsies in addition to the routine pretransplant urologic evaluation.

Diagnosis and management of the urologic complications of renal transplantation.

669 patients who received a renal transplant from January 1988 to December 1993 at a single institution were evaluated for urologic complications. Urologic complications were assessed and categorized by organ involvement: kidney, ureter, bladder, lymphatic, calculus and complicated urinary tract infection. Complications were also classified as "early" if they occurred within 14 d after transplant and those diagnosed after this period were called "late." The management of all complications is presented. There were a total of 98 urologic complications identified in 669 patients, of which 51 were complicated urinary tract infections. The other 47 complications were divided among renal (8), ureteral (19), bladder (3), lymphatic (10) and calculi (7). Preventive measures, such as technical management of ureteral reimplantation, periodic renal scan or ultrasound examinations, and long-term urinary antibiotic prophylaxis could further reduce the incidence of urologic complications. The result should be further improvement in transplant patient and graft survival.

The hematologic toxicity of interleukin-2 in patients with metastatic melanoma and renal cell carcinoma.

BACKGROUND: High dose interleukin-2 (IL-2) has been found to produce durable antitumor responses in some patients, benefiting most greatly those patients with melanoma and renal cell carcinoma. In this paper, the hematologic toxicity and changes resulting from high dose IL-2 alone administered by intravenous bolus are discussed. METHODS: One hundred ninety-nine consecutive patients treated with high dose IL-2 alone from January 1, 1988 to December 31, 1992 were included in this study. All patients had a diagnosis of metastatic melanoma or metastatic renal cell carcinoma and were treated at the National Cancer Institute (Bethesda, MD). RESULTS: Anemia, requiring erythrocyte transfusions, occurred in 14% of all treatment courses, with a median of two units of erythrocytes transfused. Severe leukopenia ( < 1,000 leukocytes/mm3) was rare (1.5% of all patients) and was not associated with any infectious complications. Severe thrombocytopenia ( < 30,000 platelets/mm3) occurred in 2.2% of all treatment cycles, with two patients experiencing a grade 3 hemorrhage, defined as gross blood loss, and one patient experiencing a grade 4 hemorrhage, defined as a debilitating blood loss. Defects in the coagulation pathway were common: abnormal partial thromboplastin time and prothrombin time values occurred in 64% and 25% of the treatment cycles, respectively. In addition, a mean clearance of 93% of lymphocytes from the peripheral blood was observed within 24 hours after initiating IL-2 therapy. This was followed by rebound lymphocytosis to a mean of 198% of baseline on posttreatment Day 4. There were no treatment-related deaths. CONCLUSIONS: During IL-2 therapy, adverse sequelae of anemia, thrombocytopenia, coagulopathy, and leukopenia were usually mild, transient and rarely limited therapy. A profound decrease in lymphocytes in the peripheral circulation occurred within 24 hours after initiating therapy, with a rebound occurring after stopping IL-2. No specific hematologic parameter was associated significantly with a patient's increased probability of responding to therapy.