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.

Induction chemotherapy is the first-line treatment for pediatric patients with hematologic malignancies. However, several complications may arise, mainly infections and febrile neutropenia, with a strong impact on patient morbidity and mortality. Such complications have been shown to be closely related to alterations of the gut microbiome (GM), making the design of strategies to foster its eubiosis of utmost clinical importance. Here, we evaluated the impact of oral supplementation of lactoferrin (LF), a glycoprotein endowed with anti-inflammatory, immunomodulatory and antimicrobial activities, on GM dynamics in pediatric oncohematologic patients during induction chemotherapy. Specifically, we conducted a double blind, placebo-controlled trial in which GM was profiled through 16S rRNA gene sequencing before and after two weeks of oral supplementation with LF or placebo. LF was safely administered with no adverse effects and promoted GM homeostasis by favoring the maintenance of diversity and preventing the bloom of pathobionts (e.g., Enterococcus). LF could, therefore, be a promising adjunct to current therapeutic strategies in these fragile individuals to reduce the risk of GM-related complications.

Cardiotoxic effects of anthracycline therapy are a major cause of morbidity for childhood cancer survivors. The aim of this retrospective evaluation is to assess the efficacy of Tissue Doppler Imaging in the early detection of myocardial alterations in these patients. A population of 50 childhood cancer survivors (32 males and 18 females) who have been treated with anthracyclines was evaluated by standard and TDI echocardiographic examination of the basal and median region of the interventricular septum (IVSb, IVSm), of the left ventricular posterior wall (LVPWb, LVPWm), and of the mitral annulus; the results were compared with those obtained from a population of 50 healthy age-matched and sex-matched controls by using the Student test. The clinical and echocardiographic data of the two groups were compared also with the independent samples t-test. All data were expressed as mean ± standard deviation. A two-tailed P-value < 0.05 was considered statistically significant. Statistical analysis was performed using STATA 7.0. The case-control analysis showed statistically significant differences (p < 0,05) between the patients and the controls values. The systolic performance of the patients was normal (LVEF (p = 0,0029) and LVFS (p = 0,0002)). Statistically significant differences between patients and controls were found for diastolic function measurements obtained with PW Doppler such as IVRT (p = 0,0000), DT (p = 0,0041), E (p = 0,0000), A (p = 0,0458), even if E/A ratio was not altered. TDI analysis also show significant differences between patients and controls in both LVPW and IVS (basal and middle segments); E/E’ ratio and E’/A’ ratio did not vary significantly. Linear Regression and multivariate analysis showed that Hematopoietic Stem Cell Transplantation had the highest impact on our measurements. The results showed a myocardial diastolic impairment with preserved ejection fraction. Since the median follow-up time of our cohort was 2 years, further evaluation is needed to better define the diastolic alterations. TDI analysis showed high sensitivity for the detection of mild myocardial dysfunction; the implementation of this novel method as standard practice in the follow-up of selected childhood cancer survivors might help to achieve a better management of long-term complications of cardiotoxic chemotherapy.

Background: Gaucher disease (GD) diagnosis can be delayed due to non-specific symptoms and lack of awareness, leading to unnecessary procedures and irreversible complications. GAU-PED study aims to assess GD prevalence in a high-risk pediatric population and the presence, if any, of novel clinical or biochemical markers associated with GD. Materials and methods: DBS samples were collected and tested for β-glucocerebrosidase enzyme activity for 154 patients selected through the algorithm proposed by Di Rocco et al. Patients showing β-glucocerebrosidase activity below normal values were recalled to confirm the enzyme deficiency with the gold standard essay on cellular homogenate. Patients tested positive at the gold standard analysis were evaluated through GBA1 gene sequencing. Results: 14 out of 154 patients were diagnosed with GD, with a prevalence of 9.09% (5.06–14.78%, CI 95%). Hepatomegaly, thrombocytopenia, anemia, growth delay/deceleration, elevated serum ferritin, elevated Lyso-Gb1 and chitotriosidase were significantly associated with GD. Conclusions: GD prevalence in a pediatric population at high-risk appeared to be higher compared to high-risk adults. Lyso-Gb1 was associated with GD diagnosis. The algorithm proposed by Di Rocco et al. can potentially improve the diagnostic accuracy of pediatric GD, allowing the prompt start of therapy, aiming to reduce irreversible complications.

Background: Food safety practices are widely recommended for pediatric patients with cancer or undergoing hematopoietic stem cell transplantation (HCT) to mitigate foodborne infectious risks. However, specific measures, such as the neutropenic diet (ND) or low‐microbial diet, lack robust evidence and are inconsistently implemented across pediatric hematology‐oncology centers. Additionally, data on foodborne illnesses (FBI) in this population remain scarce.Procedure: We conducted an online survey and a retrospective review of FBI cases across 22 centers within the Italian Association of Pediatric Hematology and Oncology (AIEOP) network, 13/22 performing allogeneic HCT.Results: All centers provide dietary recommendations to the patients. Restrictive diets are recommended in 72% of centers during hospitalization and in 77% after discharge. Universally avoided foods include unpasteurized milk, fresh fruit without skin, moldy cheeses, bakery and ice cream products, raw eggs and derivatives, raw meat, raw or smoked fish, cured meats, shellfish, and cooked food leftovers. Fresh fruits and vegetables are commonly restricted only to patients undergoing allogeneic HCT. Ninety‐five percent of centers provide patients and their families with guidelines on cleaning food at home, including thorough cleaning of fruits and vegetables with a food disinfectant. Seven centers reported FBI cases, with eight documented cases, including two fatalities caused by meningoencephalitis related to infections from Listeria monocytogenes and Bacillus cereus, respectively.Conclusions: This study highlights the need for standardized, evidence‐based food safety guidelines and FBI management to enhance care for pediatric patients receiving chemotherapy or HCT.

The gut microbiome (GM) has emerged in the last few years as a main character in several diseases. In pediatric oncological patients, GM has a role in promoting the disease, modulating the effectiveness of therapies, and determining the clinical outcomes. The therapeutic course for most pediatric cancer influences the GM due to dietary modifications and several administrated drugs, including chemotherapies, antibiotics and immunosuppressants. Interestingly, increasing evidence is uncovering a role of the GM on drug pharmacokinetics and pharmacodynamics, defining a bidirectional relationship. Indeed, the pediatric setting presents some contrasts with respect to the adult, since the GM undergoes a constant multifactorial evolution during childhood following external stimuli (such as diet modification during weaning). In this review, we aim to summarize the available evidence of pharmacomicrobiomics in pediatric oncology.