A multivariate analysis of pre-, peri-, and post-transplant factors affecting outcome after pediatric liver transplantation.

OBJECTIVE: The purpose of this study was to identify significant, independent factors that predicted 6 month patient and graft survival after pediatric liver transplantation. SUMMARY BACKGROUND DATA: The Studies of Pediatric Liver Transplantation (SPLIT) is a multicenter database established in 1995, of currently more than 4000 US and Canadian children undergoing liver transplantation. Previous published analyses from this data have examined specific factors influencing outcome. This study analyzes a comprehensive range of factors that may influence outcome from the time of listing through the peri- and postoperative period. METHODS: A total of 42 pre-, peri- and posttransplant variables evaluated in 2982 pediatric recipients of a first liver transplant registered in SPLIT significant at the univariate level were included in multivariate models. RESULTS: In the final model combining all baseline and posttransplant events, posttransplant complications had the highest relative risk of death or graft loss. Reoperation for any cause increased the risk for both patient and graft loss by 11 fold and reoperation exclusive of specific complications by 4 fold. Vascular thromboses, bowel perforation, septicemia, and retransplantation, each independently increased the risk of patient and graft loss by 3 to 4 fold. The only baseline factor with a similarly high relative risk for patient and graft loss was recipient in the intensive care unit (ICU) intubated at transplant. A significant center effect was also found but did not change the impact of the highly significant factors already identified. CONCLUSIONS: We conclude that the most significant factors predicting patient and graft loss at 6 months in children listed for transplant are posttransplant surgical complications.

Novel response to neoadjuvant anti-PD1 therapy for a patient with retrocaval melanotic schwannoma.

Melanotic schwannoma is a rare nerve sheath tumor composed of melanin-producing Schwann cells with the potential for metastasis. These tumors can be associated with familial tumor syndromes and can cause significant symptoms related to nerve compression and mass effect. Due to the rarity of these lesions, they can be initially misidentified as melanocytomas, pigmented dermatofibrosarcoma protuberans, neurofibromas or malignant melanomas. Surgical excision is the mainstay of treatment with limited benefit from adjuvant systemic chemotherapy or radiation. Modern treatments with immune checkpoint blockade have demonstrated significant improvements in progression-free and overall survival for a variety of cancer histologies; however, anti-PD1 therapy has yet to be evaluated in patients with melanotic schwannoma. This report demonstrates a significant improvement in symptomatology and tumor stability with neoadjuvant anti-PD1 therapy for a retrocaval melanotic schwannoma initially masquerading as malignant melanoma. This report demonstrates the potential benefit of a novel therapeutic option for patients with melanotic schwannoma.

Treatment of renal allograft polyoma BK virus infection with leflunomide.

BACKGROUND: Polyoma BK virus produces an aggressively destructive nephropathy in approximately 3% to 8% of renal allografts, is associated with graft loss within one year in 35% to 67% of those infected and there is no therapy of proven efficacy. Leflunomide is an immune suppressive drug with anti viral activity in vitro and in animals. METHODS: We treated twenty-six patients with biopsy proven NK virus nephropathy (BKN) with either leflunomide alone (n=17) or leflunomide plus a course of cidofovir (n=9) and followed them for six to forty months. Leflunomide was dosed to a targeted blood level of active metabolite, A77 1726, of 50 microg/ml to 100 microg/ml (150 microM to 300 microM). Response to treatment was gauged by serial determinations of viral load in blood and urine (PCR), serum creatinine, and repeat allograft biopsy. RESULTS: In the 22 patients consistently sustaining the targeted blood levels of active drug, blood and urine viral load levels uniformly decreased over time (P<.001). Mean serum creatinine levels stabilized over the first six months of treatment, and with 12 months or more of follow-up in 16 patients the mean serum creatinine has not changed significantly from base line. Four patients who did not consistently have blood levels of active drug (A77 1726) above 40 microg/ml did not clear the virus until these levels were attained or cidofovir was added. CONCLUSIONS: Leflunomide inhibits Polyoma virus replication in vitro and closely monitored leflunomide therapy with specifically targeted blood levels appears to be a safe and effective treatment for Polyoma BK nephropathy.

Open-heart surgery in pediatric patients with end-stage liver disease.

Little is known about the safety of pediatric cardiac surgery in children with end-stage liver disease. We reviewed our experience with 4 patients with biliary atresia or Alagille's syndrome who underwent repair of ventricular septal defect and tricuspid regurgitation, atrioventricular canal, subaortic stenosis, or supravalvular aortic stenosis. One patient died on postoperative day 2. All other patients survived to discharge. At follow-up, 1 patient died at home awaiting liver transplantation and the remaining patients are doing well. One patient received a successful liver transplant. Pediatric cardiac surgery in children with end-stage liver disease can be done safely, albeit with a higher mortality.