Faculty Bibliography

OBJECTIVE:Famotidine is a commonly used agent in pediatric intensive care units. There is no data regarding the safety of undiluted intravenous push (IVP) administration in pediatrics; however, there are historical concerns for hemodynamic instability in the adult population. This study assesses the safety of famotidine administered undiluted IVP for doses ≥ 5 mg in pediatric patients. METHODS:We performed a retrospective, observational, medication use evaluation in pediatric patients (≤ 18 years) who received famotidine undiluted IVP from February to July 2022. Patients with arterial lines and continuous cardiac telemetry were included. Patients requiring extracorporeal membrane oxygenation, receiving famotidine doses < 5 mg, or who had a change in vasoactive medication doses within 1 hour prior to famotidine IVP administration were excluded. The primary outcome was the incidence of hypotension and bradycardia within 45 minutes of undiluted famotidine IVP administration. RESULTS:A total of 59 patients were included. There were 8 patients (13.6%) with hypotension and 1 patient (1.7%) with bradycardia after famotidine administration in the full cohort. Of these 9 patients, 7 had hypotension and bradycardia at baseline. Two patients (3.4%) required adjustment of their vasoactive medication within 45 minutes after receiving famotidine, although these patients were also postoperative day zero from cardiac surgery. None of the patients required a fluid bolus for hypotension following famotidine administration. The percent change in hemodynamics from baseline were minimal across the various time intervals. CONCLUSION/CONCLUSIONS:Famotidine administered undiluted IVP produced no clinically significant hemodynamic -adverse effects in critically ill pediatric patients.

The backbone induction therapy for primary central nervous system lymphoma (PCNSL) is high dose methotrexate (HD-MTX) and rituximab, which can be combined with other chemotherapeutic agents. The optimal dose of HD-MTX remains unclear, as doses between 3 and 8 g/m² have been shown to be effective. In this retrospective study, HD-MTX dosed at 3-5 g/m² demonstrated an overall response of 81.8%, with 11 (50%) complete responses. The median overall survival was not met at 29 months and median progression free survival was 12.5 months.There were two discontinuations due to nephrotoxicity. The most common adverse event was hepatotoxicity (18.5%), with no treatment-related mortality events observed.Overall, HD-MTX dosed at 3-5 g/m² demonstrated similar efficacy and lower toxicity compared to higher doses in PCNSL patients. Reducing the initial HD-MTX dose may help ensure tolerability and completion of induction therapy, especially in patients with co-morbidities or older age who have poorer outcomes.

Renal vein thrombosis is the most common non-catheter-associated venous thromboembolism event in neonates, accounting for up to 20% of cases. Although mortality rates are lower than a variety of other forms of pediatric thrombosis, renal vein thrombi are associated with significant short-term and long-term sequelae. This report presents the case of a full-term neonate presenting with bilateral renal vein thrombosis with inferior vena cava involvement treated with catheter-directed thrombolysis. This case report intends to highlight the value of a multidisciplinary approach to pediatric venous thromboembolism and to outline relevant procedural details and current laboratory and imaging monitoring of catheter-directed thrombolysis.

Leukemia, most commonly B-cell acute lymphoblastic leukemia (B-ALL), accounts for about 30% of childhood cancer diagnoses. While there have been dramatic improvements in childhood ALL outcomes, certain subgroups-particularly those who relapse-fare poorly. In addition, cure is associated with significant short- and long-term side effects. Given these challenges, there is great interest in novel, targeted approaches to therapy. A number of new immunotherapeutic agents have proven to be efficacious in relapsed or refractory disease and are now being investigated in frontline treatment regimens. Blinatumomab (a bispecific T-cell engager that targets cluster of differentiation [CD]-19) and inotuzumab ozogamicin (a humanized antibody-drug conjugate to CD22) have shown the most promise. Chimeric antigen receptor T (CAR-T) cells, a form of adoptive immunotherapy, rely on the transfer of genetically modified effector T cells that have the potential to persist in vivo for years, providing ongoing long-term disease control. In this article, we discuss the clinical biology and treatment of B-ALL with an emphasis on the role of immunotherapy in overcoming the challenges of conventional cytotoxic therapy. As immunotherapy continues to move into the frontline of pediatric B-ALL therapy, we also discuss strategies to address unique side effects associated with these agents and efforts to overcome mechanisms of resistance to immunotherapy.