Venetoclax in combination with chemotherapy as treatment for pediatric advanced hematologic malignancies.

BACKGROUND: Venetoclax is frequently used as salvage treatment in pediatric, adolescent, and young adult (AYA) patients with advanced hematologic malignancies. However, more data are needed from real-world studies to guide the safe and appropriate use of venetoclax in this population. PROCEDURE: We retrospectively reviewed the medical records of all patients diagnosed with hematologic malignancies less than 30 years of age treated with venetoclax outside of clinical trials at the University of California San Francisco Benioff Children's Hospitals from 2016 to 2022. RESULTS: We identified 13 patients (acute myeloid leukemia, n = 8; B-acute lymphoblastic leukemia, n = 3; myelodysplastic syndrome, n = 2) aged 4 months to 27 years. A median of 3 prior lines of therapy weregiven (range 0-5). All patients received venetoclax in combination with either a hypomethylating agent or conventional chemotherapy. Three (23%) patients achieved complete remission (CR); two (15%) achieved partial remission (PR); 3 (23%) had stable disease (SD), and five (42%) had progressive disease. Median survival and time to progression from venetoclax initiation was 9 months (range 2.5-52 months) and 3 months (range 2 weeks to 7.5 months), respectively. Six patients (46%) developed grade 3 or higher infections while receiving venetoclax, including bacteremia due to atypical organisms, invasive pulmonary infections with Aspergillus, cytomegalovirus (CMV) viremia, skin infections, and encephalitis with bacterial brain abscesses. CONCLUSIONS: Venetoclax in combination with hypomethylating agents or cytotoxic chemotherapy was effective in a subset of pediatric/AYA patients with advanced hematologic malignancies, but multiple severe infections were observed, particularly among patients who received venetoclax in combination with chemotherapy. Prospective studies will be required to determine the optimal dose and duration of venetoclax in this population.

Molecular epidemiology of Clostridioides difficile in domestic dogs and zoo animals.

Animals such as domestic dogs and zoo animals reside in close proximity to humans and could contribute to the dissemination of Clostridioides difficile spores which are common in the community environment. The purpose of this study was to assess C. difficile colonization in domestic dogs attending a day boarding facility and zoo animals receiving systemic antibiotics. Stool samples and paw swabs were collected from dogs who attended a day boarding facility. Stool samples were also collected from zoo animals starting systemic antibiotics. Finally, environmental samples were collected from nearby public parks. Stool samples and swabs were incubated anaerobically in enrichment broth for C. difficile growth, PCR was done to confirm presence of toxin genes, and PCR ribotyping was performed for strain characterization. During the study period, 136 dog stool samples were obtained, the paws of 16 dogs were swabbed, and 250 environmental swabs from surrounding public parks were obtained. Twenty-three of 136 dog stool samples (17%) and 9 of 16 dog paws sampled (56%) grew toxigenic C. difficile. One hundred and four stool samples from 49 zoo animals were collected of which 19 (18%) grew toxigenic C. difficile. Rates of toxigenic C. difficile colonization increased significantly during antibiotic therapy (33%) and then returned to baseline during the follow-up (11%) period (p = 0.019). Fifty-five of 250 environmental swabs from public parks (22%) grew toxigenic C. difficile. Ribotypes associated with human disease including 106 and 014-020 were isolated from all sources. This study demonstrated a high rate of toxigenic C. difficile colonization in domestic dogs and zoo animals with ribotypes similar to those causing human disease. These results demonstrate the relationship between humans, animals, and the environment in the dissemination of spores.