The correlation existing between gut microbiota diversity and survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has so far been studied in adults. Pediatric studies question whether this association applies to children as well. Stool samples from a multicenter cohort of 90 pediatric allo-HSCT recipients were analyzed using 16S ribosomal RNA amplicon sequencing to profile the gut microbiota and estimate diversity with the Shannon index. A global-to-local networking approach was used to characterize the ecological structure of the gut microbiota. Patients were stratified into higher- and lower-diversity groups at 2 time points: before transplantation and at neutrophil engraftment. The higher-diversity group before transplantation exhibited a higher probability of overall survival (88.9% ± 5.7% standard error [SE] vs 62.7% ± 8.2% SE; P = .011) and lower incidence of grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (aGVHD). No significant difference in relapse-free survival was observed between the 2 groups (80.0% ± 6.0% SE vs 55.4% ± 10.8% SE; P = .091). The higher-diversity group was characterized by higher relative abundances of potentially health-related microbial families, such as Ruminococcaceae and Oscillospiraceae. In contrast, the lower-diversity group showed an overabundance of Enterococcaceae and Enterobacteriaceae. Network analysis detected short-chain fatty acid producers, such as Blautia, Faecalibacterium, Roseburia, and Bacteroides, as keystones in the higher-diversity group. Enterococcus, Escherichia-Shigella, and Enterobacter were instead the keystones detected in the lower-diversity group. These results indicate that gut microbiota diversity and composition before transplantation correlate with survival and with the likelihood of developing aGVHD.

CBL plays a key role in different cell pathways, mainly related to cancer onset and progression, hematopoietic development and T cell receptor regulation. Somatic CBL mutations have been reported in a variety of malignancies, ranging from acute myeloid leukemia to lung cancer. Growing evidence have defined the clinical spectrum of germline CBL mutations configuring the so-called CBL syndrome; a cancer-predisposing condition that also includes multisystemic involvement characterized by variable phenotypic expression and expressivity. This review provides a comprehensive overview of the molecular mechanisms in which CBL exerts its function and describes the clinical manifestation of CBL mutations in humans.

Antimicrobial stewardship programs represent efficacious measures for reducing antibiotic overuse and improving outcomes in different settings. Specific data on pediatric oncology are lacking. We conducted a systematic review on the PubMed and Trip databases according to the PRISMA guidelines, searching for reports regarding antimicrobial stewardship in pediatric oncology and hematology patients. The aim of the study was to summarize the present literature regarding the implementation of antimicrobial stewardship programs or initiatives in this particular population, and provide insights for future investigations. Nine papers were included in the qualitative analysis: three regarding antifungal interventions, five regarding antibacterial interventions, and one regarding both antifungal and antibacterial stewardship interventions. Variable strategies were reported among the included studies. Different parameters were used to evaluate the impact of these interventions, including days of therapy per 1000-patient-days, infections with resistant strains, safety analysis, and costs. We generally observed a reduction in the prescription of broad-spectrum antibiotics and an improved appropriateness, with reduced antibiotic-related side effects and no difference in infection-related mortality. Antibiotic stewardship programs or interventions are effective in reducing antibiotic consumption and improving outcomes in pediatric oncology hematology settings, although stewardship strategies differ substantially in different institutions. A standardized approach needs to be implemented in future studies in order to better elucidate the impact of stewardship programs in this category of patients.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a potentially curative strategy for many oncological and non-oncological diseases, but it is associated with marked morbidity and mortality. The disruption of gut microbiota (GM) eubiosis has been linked to major allo-HSCT complications, including infections and acute graft vs. host disease (aGvHD), and correlates with mortality. This increasing knowledge on the role of the GM in the allo-HSCT procedure has led to fascinating ideas for modulating the intestinal ecosystem in order to improve clinical outcomes. Nutritional strategies, either by changing the route of nutritional supplementation or by administering specific molecules, are increasingly being considered as cost- and risk-effective methods of modulating the GM. Nutritional support has also emerged in the past several years as a key feature in supportive care for allo-HSCT recipients, and deterioration of nutritional status is associated with decreased overall survival and higher complication rates during treatment. Herein we provide a complete overview focused on nutritional modulation of the GM in allo-HSCT recipients. We address how pre transplant diet could affect GM composition and its ability to withstand the upsetting events occurring during transplantation. We also provide a complete overview on the influence of the route of nutritional administration on the intestinal ecosystem, with a particular focus on the comparison between enteral and parenteral nutrition (PN). Moreover, as mounting evidence are showing how specific components of post-transplant diet, such as lactose, could drastically shape the GM, we will also summarize the role of prebiotic supplementation in the modulation of the intestinal flora and in allo-HSCT outcomes.

Patients with hematological malignancies (HM) or undergoing hematopoietic cell transplantation (HCT) face high risk of bloodstream infections (BSI) during febrile neutropenia. Rising antimicrobial resistance (AMR), especially among Gram-negative (GN) bacteria, challenges effective empirical antibiotic therapy (EAT) selection. This ECIL-10 systematic review updates European resistance epidemiology since the 2011 ECIL-4 guidelines publication to inform clinical recommendations. We conducted a systematic review (ID: CRD42025638003) of bacterial epidemiology and resistance in HM/HCT patients across Europe, from June 2011 to September 2024 using PubMed, Embase, and Web of Science according to PRISMA guidelines. We included studies reporting BSI or colonization rates and resistance patterns, including extended-spectrum beta-lactamase-producing/third-generation cephalosporin-resistant (ESBL/3GCR), fluoroquinolone-resistant (FQ-R) carbapenem-resistant (CR), and multidrug-resistant (MDR) for GN bacteria; methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) for Gram-positive (GP) bacteria. Two reviewers independently extracted data with ECDC/EARS-Net surveillance 2011 and 2022 data providing supporting analysis. We examined fluoroquinolone prophylaxis (FQ-P) impact on BSI rate and resistance. Analysis included 40 studies (33,387 patients/febrile episodes from observational studies and 21,402 patients from one meta-analysis) across 12 European countries. BSI prevalence averaged 30% (range, 15-59%), with 42% GN and 51% GP distribution. Median resistance rates among GN BSI were: 55% for FQ-R, 30% for ESBL/3GCR, 13% for both CR and MDR. CR reached 26% in P. aeruginosa (PsA) and 38% in K. pneumoniae (KPn). Among GP BSI resistance was 3% for MRSA and 1% for VRE. Colonization studies demonstrated 20% ESBL/3GCR and 5% CR rates. We identified a southeastern European resistance gradient and significant temporal increase in ESBL/3GCR, CR KPn, and MDR PsA, confirmed in ECDC/EAR-Net analysis. FQ-P reduced overall and GN BSI incidence but increased FQ-R and ESBL/3GCR GN infections in adults. In children, FQ-P reduced BSI in leukemia but not in HCT and data on resistance were inconclusive. ECIL-10 proposed resistance reporting aligned with ESCMID/IDSA guidelines. AMR presents an escalating challenge in febrile neutropenic HM/HCT patients with geographical variability and increasing resistance trends. These findings strongly support the need for updated guidelines, antimicrobial stewardship programs, rapid diagnostics implementation, and prospective studies to optimize effective empirical therapy strategies.