Alterations in a Consecutive Childhood B-Cell Acute Lymphoblastic Leukemia Cohort Treated Using the ALL IC-BFM 2009 Protocol.

In this study, we aimed to identify patients within our B-ALL cohort with altered . Our objective was to use a comprehensive analysis approach to characterize the types of genetic changes, determine their origin (somatic/germline), and analyze the clinical outcomes associated with them. A consecutive cohort of 99 patients with B-ALL treated at the Children's Hospital of the UMC Ljubljana according to the ALL IC-BFM 2009 protocol was included in our study.

Paediatric Medical Traumatic Stress in Children with Cancer and their Parents: Difference in Stress Levels Due to Illness and Treatment Factors.

Pediatric medical traumatic stress (PMTS) is a set of children's and their parents' psychological and physiological responses to pain, injuries, serious illnesses, and other experiences with the medical environment. Pediatric cancer patients have the highest prevalence of PMTS as the illness its treatment involve a set of stressors that trigger many negative psychological reactions. The current study examined the difference in levels of traumatic stress in children with cancer and their parents due to medical factors (type of cancer, outcome, duration, and intensity of treatment, time since diagnosis, relapse, and hospitalization in ICU).

Integrative Transcriptomic Profiling of the Wilms Tumor.

Our study aimed to identify relevant transcriptomic biomarkers for the Wilms tumor, the most common pediatric kidney cancer, independent of the histological type and stage. Using next-generation sequencing, we analyzed the miRNA profiles of 74 kidney samples, which were divided into two independent groups: fresh frozen tissue and formalin-fixed paraffin-embedded tissue samples. Subsequent mRNA expression profiling and pathway analysis were performed to establish the interplay and potential involvement of miRNAs and mRNA in the Wilms tumor.

Simoctocog alfa (Nuwiq®) in previously untreated patients with severe haemophilia A-Final efficacy and safety results from the NuProtect study.

Introduction: Simoctocog alfa (Nuwiq®) is a 4th generation recombinant FVIII with proven efficacy for the prevention and treatment of bleeding episodes (BEs) in previously treated patients with severe haemophilia A. The NuProtect study assessed the immunogenicity, efficacy and safety of simoctocog alfa in 108 previously untreated patients (PUPs). The incidence of high-titre inhibitors was 16.

Immune Tolerance Induction (ITI) with a pdFVIII/VWF Concentrate (octanate) in 100 Patients in the Observational ITI (ObsITI) Study.

 Immune tolerance induction (ITI) with repeated factor VIII (FVIII) administration is the only strategy proven to eradicate inhibitors. The observational ITI study is evaluating ITI with a range of FVIII products.  This subgroup analysis reports prospective interim data for patients treated with a plasma-derived, von Willebrand factor-stabilized FVIII concentrate (pdFVIII/VWF, octanate).

Toxicity and Clinical Results after Proton Therapy for Pediatric Medulloblastoma: A Multi-Centric Retrospective Study.

Medulloblastoma is the most common malignant brain tumor in children. Even if current treatment dramatically improves the prognosis, survivors often develop long-term treatment-related sequelae. The current radiotherapy standard for medulloblastoma is craniospinal irradiation with a boost to the primary tumor site and to any metastatic sites.

Clinical impacts of copy number variations in B-cell differentiation and cell cycle control genes in pediatric B-cell acute lymphoblastic leukemia: a single centre experience.

Background: gene deletions have been identified as a poor prognostic factor in pediatric B-cell acute lymphoblastic leukemia (B-ALL), especially in the presence of co-occurring deletions ( profile). This study aimed to determine the frequency of deletions and deletions in other B-cell differentiation and cell cycle control genes, and their prognostic impact in Slovenian pediatric B-ALL patients.

Patients And Methods: We studied a cohort of 99 patients diagnosed with B-ALL from January 2012 to December 2020 and treated according to the ALL IC-BFM 2009 protocol.

Simoctocog Alfa (Nuwiq) in Previously Untreated Patients with Severe Haemophilia A: Final Results of the NuProtect Study.

Introduction:  FVIII inhibitor development is the most serious contemporary treatment complication in haemophilia A, particularly in previously untreated patients (PUPs). No inhibitors developed in clinical trials in previously treated patients treated with simoctocog alfa (Nuwiq), a fourth-generation recombinant FVIII produced in a human cell line.

Methods:  The NuProtect study investigated the immunogenicity of simoctocog alfa in PUPs.

von Willebrand factor alloantibodies in type 3 von Willebrand disease.

: The development of neutralizing antibodies is a rare complication of von Willebrand disease treatment. In major surgical procedures for severe forms of the disease, the recognition of ineffective therapy and alternative treatment protocols are lifesaving. We report the case of a 6-year-old girl with type 3 von Willebrand disease in whom inhibitors were sought due to ineffective haemostasis together with lower than expected von Willebrand factor (VWF) recoveries after a surgical procedure.

Development of the SIOPE DIPG network, registry and imaging repository: a collaborative effort to optimize research into a rare and lethal disease.

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG.

Low-dose continuous infusion of factor VIII in patients with haemophilia A.

Background: Patients with haemophilia A (HA) or B (HB) can be given prophylactic or on-demand treatment administered by continuous infusion or bolus injections of factor VIII (FVIII) or IX (FIX). In this study we evaluated the efficacy and safety of low-dose continuous infusion of FVIII or FIX.

Material And Methods: We studied all eligible patients with HA or HB treated with continuous infusion of factor concentrates over an 18-year period in a single Slovenian Haemophilia Comprehensive Care Centre.

First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study.

Introduction/background: Development of neutralizing inhibitors against factor VIII (FVIII) is a major complication of haemophilia A treatment.

Aim: The ongoing, international, open-label, uncontrolled, observational immune tolerance induction (ObsITI) study evaluates ITI, the standard of care in patients with inhibitors.

Patients/methods: Forty-eight prospective patients in this interim analysis received a single plasma-derived, von Willebrand factor-stabilized, FVIII concentrate (pdFVIII/VWF) for ITI.

Diagnostic accuracy of lipopolysaccharide-binding protein for predicting bacteremia/clinical sepsis in children with febrile neutropenia: comparison with interleukin-6, procalcitonin, and C-reactive protein.

Purpose: In febrile neutropenia (FN), no reliable marker has been identified to discriminate between severe infection and other causes of fever early in the clinical course. Since lipopolysaccharide-binding protein (LBP) has proven to be an accurate biomarker of bacteremia/clinical sepsis in critically ill non-immunocompromised infants and children, we performed a prospective study to determine the diagnostic accuracy of LBP in children with FN.

Methods: Concentrations of LBP, procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) were prospectively measured on two consecutive days in 90 FN episodes experienced by 47 children.

Treatment of severe human metapneumovirus (hMPV) pneumonia in an immunocompromised child with oral ribavirin and IVIG.

Background: The clinical manifestations of human metapneumovirus (hMPV) infection resemble those of respiratory syncytial virus with the most severe disease occurring in infants, the elderly, chronically ill, and immunocompromised hosts.

Observation: We present a case of a 2-year-old girl undergoing intensive chemotherapy for Burkitt lymphoma who developed severe hMPV pneumonia. Rapid and complete recovery was observed after treatment with oral ribavirin and intravenous immunoglobulin.

Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders.

Background: The European Network of Rare Bleeding Disorders (EN-RBD) was established to bridge the gap between knowledge and practise in the care of patients with RBDs.

Objectives: To explore the relationship between coagulation factor activity level and bleeding severity in patients with RBDs.

Patients/methods: Cross-sectional study using data from 489 patients registered in the EN-RBD.

Individualized long-term enzyme therapy for Gaucher disease type 1 in Slovenia.

Background: Gaucher disease type 1 (GD1) was the first lysosomal storage disorder for which an effective enzyme replacement therapy was developed. We describe the management of eight GD1 patients in Slovenia who were diagnosed between the ages of 2 and 15 years.

Methods: Patients were individually assessed to establish initial enzyme doses and monitored frequently to determine the effects of long-term enzyme dose regimens.

Multifocal hepatoblastoma in a 6-month-old girl with trisomy 18: a case report.

Introduction: Edward's syndrome (trisomy 18) is a rare entity with a reported incidence of 1/3000 to 1/7000 births. Less than 10% of patients survive beyond the first year of life, which may influence the fact that malignant tumors are rarely reported in association with this syndrome.

Case Presentation: The authors report a rare case of a 6-month-old girl with trisomy 18 and multifocal hepatoblastoma.