Microbiota Predict Infections and Acute Graft-Versus-Host Disease After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Despite preventive measures, infections continue to pose significant risks to pediatric allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The gut microbiota has been linked to clinical outcomes following adult allo-HCT. This study evaluated whether similar disruptions or differing microbiota patterns were associated with infection risk in pediatric allo-HCT. METHODS: In a prospective observational study, fecal samples were obtained from 74 children before conditioning and upon neutrophil recovery. Microbiome signatures identified through sequencing were examined for their associations with infections or acute graft-versus-host disease (aGVHD) in the first-year post-HCT using Cox proportional hazards analysis. RESULTS: Microbiome disruption in adults, did not predict infection risk in pediatric allo-HCT. Unique microbiota signatures were associated with different infections or aGVHD. A ratio of strict and facultative anaerobes (eg, Lachnoclostridium, Parabacteroides) prior to conditioning predicted bacteremia risk (Cox hazard ratio [HR], 3.89). A distinct ratio of oral (eg, Rothia, Veillonella) to intestinal anaerobes (eg, Anaerobutyricum, Romboutsia) at neutrophil recovery predicted likelihood of bacterial infections (Cox HR, 1.81) and viral enterocolitis (Cox HR, 1.96). CONCLUSIONS: Interactions between medical interventions, pediatric hosts, and microbial communities contribute to microbiota signatures that predict infections. Further multicenter study is necessary to validate the generalizability of these ratios as biomarkers.

Performance of Tumor Surveillance for Children With Cancer Predisposition.

Importance: Pediatric oncology patients are increasingly recognized as having an underlying cancer predisposition syndrome (CPS). Surveillance is often recommended to detect new tumors at their earliest and most curable stages. Data on the effectiveness and outcomes of surveillance for children with CPS are limited. Objective: To evaluate the performance of surveillance across a wide spectrum of CPSs. Design, Setting, and Participants: This cohort study reviewed surveillance outcomes for children and young adults from birth to age 23 years with a clinical and/or molecular CPS diagnosis from January 1, 2009, through September 31, 2021. Patients were monitored using standard surveillance regimens for their corresponding CPS at a specialty pediatric oncology center. Patients with hereditary retinoblastoma and bone marrow failure syndromes were excluded. Data were analyzed between August 1, 2021, and December 6, 2023. Exposure: Cancer predisposition syndrome. Main Outcomes and Measures: Outcomes of surveillance were reviewed to evaluate the incidence, spectrum, and clinical course of newly detected tumors. Surveillance modalities were classified for accuracy and assessed for common strengths and weaknesses. Results: A total of 274 children and young adults (mean age, 8 years [range, birth to 23 years]; 144 female [52.6%]) with 35 different CPSs were included, with a median follow-up of 3 years (range, 1 month to 12 years). During the study period, 35 asymptomatic tumors were detected in 27 patients through surveillance (9.9% of the cohort), while 5 symptomatic tumors were detected in 5 patients (1.8% of the cohort) outside of surveillance, 2 of whom also had tumors detected through surveillance. Ten of the 35 tumors (28.6%) were identified on first surveillance imaging. Malignant solid and brain tumors identified through surveillance were more often localized (20 of 24 [83.3%]) than similar tumors detected before CPS diagnosis (71 of 125 [56.8%]; P < .001). Of the 24 tumors identified through surveillance and surgically resected, 17 (70.8%) had completely negative margins. When analyzed across all imaging modalities, the sensitivity (96.4%), specificity (99.6%), positive predictive value (94.3%), and negative predictive value (99.6%) of surveillance were high, with few false-positive (6 [0.4%]) or false-negative (5 [0.3%]) findings. Conclusions and Relevance: These findings suggest that standardized surveillance enables early detection of new tumors across a wide spectrum of CPSs, allowing for complete surgical resection and successful treatment in the majority of patients.