Introduction: Diffuse intrinsic pontine glioma (DIPG) and paediatric high-grade glioma (pHGG) are aggressive glial tumours, for which conventional treatment modalities fall short. Dendritic cell (DC)-based immunotherapy is being investigated as a promising and safe adjuvant therapy. The Wilms’ tumour protein (WT1) is a potent target for this type of antigen-specific immunotherapy and is overexpressed in DIPG and pHGG. Based on this, we designed a non-randomised phase I/II trial, assessing the feasibility and safety ofWT1mRNA-loaded DC (WT1/DC) immunotherapy in combination with conventional treatment in pHGG and DIPG. Methods and analysis: 10 paediatric patients with newly diagnosed or pretreated HGG or DIPG were treated according to the trial protocol. The trial protocol consists of leukapheresis of mononuclear cells, the manufacturing of autologous WT1/DC vaccines and the combination of WT1/DC-vaccine immunotherapy with conventional antiglioma treatment. In newly diagnosed patients, this comprises chemoradiation (oral temozolomide 90 mg/m²daily+radiotherapy 54 Gy in 1.8 Gy fractions) followed by three induction WT1/DC vaccines (8–10×10⁶cells/vaccine) given on a weekly basis and a chemoimmunotherapy booster phase consisting of six 28-day cycles of oral temozolomide (150–200 mg/m²on days 1–5) and a WT1/DC vaccine on day 21. In pretreated patients, the induction and booster phase are combined with best possible antiglioma treatment at hand. Primary objectives are to assess the feasibility of the production of mRNA-electroporated WT1/DC vaccines in this patient population and to assess the safety and feasibility of combining conventional antiglioma treatment with the proposed immunotherapy. Secondary objectives are to investigate in vivo immunogenicity of WT1/DC vaccination and to assess disease-specific and general quality of life. Ethics and dissemination: The ethics committee of the Antwerp University Hospital and the University of Antwerp granted ethics approval. Results of the clinical trial will be shared through publication in a peer-reviewed journal and presentations at conferences. Trial registration number: NCT04911621

Background and Objectives: Central Nervous System (CNS) pediatric tumors represent the most common solid tumors in children with a wide variability in terms of survival and therapeutic response. By contrast to their adult counterpart, the mutational landscape of pediatric CNS tumors is characterized by oncogenic fusions rather than multiple mutated genes. CNS pediatric tumors associated with oncogenic fusions represent a complex landscape of tumors with wide radiological, morphological and clinical heterogeneity. In the fifth CNS WHO classification, there are few pediatric CNS tumors for which diagnosis is based on a single oncogenic fusion. This work aims to provide an overview of the impact of rare oncogenic fusions (NTRK, ROS, ALK, MET, FGFR, RAF, MN1, BCOR and CIC genes) on pathogenesis, histological phenotype, diagnostics and theranostics in pediatric CNS tumors. We report four cases of pediatric CNS tumors associated with NTRK (n = 2), ROS (n = 1) and FGFR3 (n = 1) oncogenic fusion genes as a proof of concept. Cases presentation and literature review: The literature review and the cohort that we described here underline that most of these rare oncogenic fusions are not specific to a single morpho-molecular entity. Even within tumors harboring the same oncogenic fusions, a wide range of morphological, molecular and epigenetic entities can be observed. Conclusions: These findings highlight the need for caution when applying the fifth CNS WHO classification, as the vast majority of these fusions are not yet incorporated in the diagnosis, including grade evaluation and DNA methylation classification.

Background and Clinical Significance: Vitamin B12 deficiency in infancy is an uncommon but reversible cause of severe hematologic abnormalities and potential neurologic injury, particularly in exclusively breastfed infants whose vitamin B12 status depends on maternal stores. Because its clinical presentation may mimic bone marrow failure syndromes or hematologic malignancies, diagnosis can be challenging and delayed; Case Presentation: We report a case of early infantile pancytopenia ultimately attributed to profound vitamin B12 deficiency secondary to maternal celiac disease. Prompt recognition and treatment with cobalamin supplementation resulted in rapid hematologic recovery and a favorable clinical outcome; Conclusions: This case underscores the importance of considering vitamin B12 deficiency in the differential diagnosis of unexplained cytopenias in infants and highlights the critical role of maternal nutritional status in neonatal health. Improved awareness and targeted screening of at-risk mothers during pregnancy and lactation may prevent severe but readily treatable complications in affected infants.

Diffuse hemispheric glioma, H3G34-mutant (H3G34-DHG) is a rare, highly malignant brain tumour with a dismal prognosis and a median time to progression (TTP) of 10 months with best available practice. We report a case of a 13-year-old boy with H3G34-DHG who underwent a multimodal treatment strategy, combining backbone chemotherapy, radiotherapy, surgery, tumour treating fields with Wilms Tumour-1 (WT1) directed dendritic cell immunotherapy and targeted therapy (STAT3-inhibition). The patient had a TTP of 787 days or 25 months, more than double the literature-reported median, with preserved quality of life and showing downregulation of WT1. This case supports the feasibility of combining multiple therapeutic modalities in the management of high-risk paediatric brain tumours, with potential synergy between different treatment elements. While access to novel therapies in the context of clinical trials remains essential, this case illustrates how treatment can be tailored to individual tumour biology and tolerability. The rationale presented in this detailed case report can inform future trial designs and promote precision medicine approaches for this tumour type.

Vitamin B12 deficiency in infancy is an uncommon but reversible cause of severe hema-tologic abnormalities and potential neurologic injury, particularly in exclusively breastfed infants whose vitamin B12 status depends on maternal stores. Because its clinical presentation may mimic bone marrow failure syndromes or hematologic malignancies, diagnosis can be challenging and delayed. We report a case of early infantile pancytopenia ultimately attributed to profound vitamin B12 deficiency secondary to maternal celiac disease. Prompt recognition and treatment with cobalamin supplementation resulted in rapid hematologic recovery and favorable clinical outcome. This case underscores the importance of considering vitamin B12 deficiency in the differ-ential diagnosis of unexplained cytopenias in infants and highlights the critical role of maternal nutritional status in neonatal health. Improved awareness and targeted screen-ing of at-risk mothers during pregnancy and lactation may prevent severe but readily treatable complications in affected infants.