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Abstract Preliminary evidence suggests perturbations of the kynurenine pathway (KP) of tryptophan metabolism in infants with single ventricle heart disease (SVHD). In 72 infants with SVHD undergoing stage 2 palliation (S2P) and 41 controls, we quantified serum KP metabolite concentrations via tandem mass spectroscopy pre‐S2P and post‐S2P at 2, 24, and 48 h and assessed metabolite relationships with post‐S2P outcomes (length of stay, hypoxemia burden, and intubation duration). Pre‐S2P, SVHD infants had lower tryptophan and serotonin levels and higher kynurenic acid, 3‐hydroxykynurenine, and picolinic acid levels than controls. Post‐S2P, metabolites peaked at 2 h, with return to baseline by 48 h for all except kynurenic acid, which remained elevated. Metabolite concentrations pre‐S2P were poorly associated with outcomes. A lower serotonin peak 2 h post‐S2P was associated with longer length of stay and intubation duration. Multiple metabolites at 24 and 48 h correlated with outcomes; notably, elevated kynurenic acid was associated with worse results for all three outcomes. Our results confirm that interstage SVHD infants have altered KP activity compared to controls. Further, the link between outcomes and KP metabolites post‐S2P—but not at baseline—demonstrates that acute, perioperative changes in tryptophan catabolism may be more important to tolerating S2P physiology than chronic interstage changes.

Abstract Background The time‐limited combination of venetoclax and obinutuzumab (VenG) was established by the German CLL Study Group in the CLL14 trial for the upfront management of newly diagnosed chronic lymphocytic leukemia (CLL), showing a superior progression free survival benefit. The incidence of grade 3–4 neutropenia was reported in the range of 52.8%–57.7%. However, patients who develop neutropenia with this combination have yet to be formally characterized in the literature as it has impact on the clinical practice setting. Aim To determine the incidence of grade 3 and 4 neutropenia and identify risk factors for neutropenia among CLL patients treated with the VenG regimen. Methods We conducted a retrospective, single‐center study of all adult patients with a diagnosis of CLL treated with VenG at the University of Colorado Hospital. Demographic information, laboratory data, clinical data, and medication prescriptions were collected from the patients' electronic medical record. Results A total of 14 patients (73%) developed neutropenia during the course of therapy. The mean time to neutropenia from the start of treatment was 42 days (range 1–131). Our cohort harbored more high risk disease features and more comorbidities (CIRS score of 12). Four patients (28.6%) in the neutropenic group developed infectious complications during therapy and 6 (31%) patients were unable to be dose escalated to the final FDA approved dose of 400 mg. Conclusion Our study cohort had higher incidence of grade 3 and 4 neutropenia occurring in 73% of patients. This could be attributed to a higher rate of comorbidities, high risk features, concomitant interacting medications, and prior chemotherapy. Further studies are warranted to determine if growth factor support is efficacious to achieve dose escalation with this therapy.