Background: Recent advances in childhood acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL) management provide higher survival rates at the cost of increased toxicities. Acute neurotoxicity affects up to 10% of patients, requiring rapid recognition and treatment. Methods: A retrospective observational study was performed to determine the frequency, clinical manifestations, radiological characteristics, treatment options and outcome of acute neurological adverse events in pediatric patients with lymphoid malignancies at the Department of Oncology and Hematology, Children’s Hospital Zagreb, Croatia. Results: A total of 56 patients (48 ALL and 8 LL, male/female ratio 1:1, average age 5.4 years) were treated mainly according to the ALL-IC BFM 2009 protocol. The B-immunophenotype was the most frequent (85.7%). Most patients were stratified to the intermediate risk group (39.3%), and two were initially diagnosed with central nervous system infiltration. Acute neurotoxic events were registered in 11 patients (19.6%), most commonly in the 6–10-year age group (66.7%), predominately in females (72.7%) and high-risk group (54.5%). The most frequent clinical presentation was seizures (83.3%), with status epilepticus in four cases. We detected electroencephalogram (EEG) irregularities in almost all patients and various morphological changes in the brain magnetic resonance imaging (MRI), most often consistent with posterior reversible encephalopathy syndrome and leukoencephalopathy. Approximately half the patients received prolonged antiepileptic therapy. No apparent residual neurologic manifestations have been observed. Conclusions: Acute neurotoxicity is a rather frequent treatment-related adverse event, associated with high-risk disease. Early recognition and timely management are essential for rapid recovery and optimal outcomes.

Malnutrition is often observed in pediatric cancer patients and has been recognized as a risk factor for relapse and survival. Maintaining an appropriate nutritional status during anticancer treatment has, therefore, been more and more frequently perceived as an additional requirement for optimal therapy outcomes. The aim of our study was to establish alterations of nutritional status in 26 children and adolescents treated for acute lymphoblastic leukemia (ALL) at the Children’s Hospital in Zagreb, Croatia, between 2016 and 2021, by using anthropometric measures and serum albumin levels. The majority of patients (53.8% female, median 4 years, 52.2% intermediate-risk leukemia group) had normal weight at the beginning of chemotherapy. The percentage of overweight/obese patients increased from 4.2% at diagnosis to 37.5% at the end of intensive therapy. Apart from a significant increase in body weight (BW) and body mass index (BMI) for age, a notable decline in body height/body length (BH/BL) for age in the observed period was recorded, especially in high-risk leukemia patients. The alterations in serum albumin values were not significant, nor was their correlation with BMI. Dietary consultation was offered to all patients, while children with a decline in BMI and BH/BL received additional nutritional support.

Iron deficiency anemia (IDA) continues to be a global public health concern, mostly in the developing countries. However, precise epidemiological data on childhood IDA in Croatia are lacking. In order to establish its frequency, underlying etiologies, the rationale for tertiary care visits, diagnostic practices, and current treatment regimens of IDA, medical records of children referred to pediatric hematologists for iron deficiency in a five-year period at tertiary institutions (Zagreb, Rijeka, Split, Osijek) throughout Croatia were retrospectively analyzed. Eight hundred and sixty-four children, predominately of preschool age, were referred mainly by the primary care pediatricians, who, in general, performed basic diagnostics but failed to initiate oral iron therapy in half of the patients. Approximately one-third of patients were symptomatic, with inadequate nutrition prevailing as underlying etiology. Dextriferron was the preferred iron formulation among hematologists, with a median dose of 5 mg/kg, with acceptable compliance rates (63.5–93.2%). Hospital admission rates varied among the centers (9.4–35%), and so did transfusion policies (6.4–22.9%). The greatest difference was observed in the frequency of parenteral iron administration (0.3–21.5%). In conclusion, the burden of childhood IDA, even in a high-income country, remains substantial, necessitating consistent implementation of national guidelines and additional education of primary health care providers.

We report our center experience in immunotherapy of high risk neuroblastoma, in particular concerning the most common side effects and their management. Multidisciplinary team approach will be discussed as well, as it is especially important in care for these patients. Retrospective review of hospital medical data basis High risk neuroblastoma patients receive intensive multimodal therapy that includes induction, consolidation, and postconsolidation phases. The postconsolidation or maintenance phase implies immunotherapy with anti-GD2 monoclonal antibody dinutuximab beta, applied with the purpose of eliminating any residual tumor cells that may exist after induction and consolidation treatment (multiagent chemotherapy, surgery, high-dose chemotherapy and autologous stem cell transplant). During the 3-year period (2017 – 2019) 8 high risk neuroblastoma patients received immunotherapy with dinutixumab beta in our center. Patients were in remission confirmed by different methods of investigation. Dinutuximab beta was applied in hospital conditions, as a 10-day continuous infusion, with premedication and concomitant medications that included crystalloid fluids, various pain medications, antihistamines, antiemetics and antipyretics, requiring double lumen central venous catheter and continuous monitoring of vital functions. Most of our patients achieved adequate pain control with gabapentin and titrated doses of opioids. Fever was a common side effect easily managed by NSAIDs. In case of allergic reaction the rate of dinutuximab beta was decreased by half and restored to its full rate after resolution of symptoms. In the meantime additional doses of antihistamines, oxygen, salbutamol and racemic epinephrine were applied depending on the clinical condition. Special care was dedicated to fluid balance supervision due to the risk of capillary leak syndrome. Although 5 of our patients had some degree of capillary leak, only one patient developed significant hypotension which was recognized and treated in timely manner with fluid boluses and epinephrine titrated to effect. Upon resolution of hypotension, the drug infusion was restarted at 50% rate during 2 hours and after that in the absence of recurrent hypotension increased to the full rate. Postconsolidation immunotherapy with dinutuximab beta has become the standard of care for high-risk neuroblastoma patients. The benefits of this kind of therapy do not come without risks. Having front-line providers who are familiar with immunotherapy and its associated toxicities is critical to the safe and consistent administration of this complex therapy. The team includes physicians of different specialities, nurse practitioners, physician assistants and bedside nurses.

Non-rhabdomyosarcoma soft-tissue sarcoma (“RMS-like” and “non-RMS-like” tumours- NRSTS) of childhood is a highly heterogeneous group of tumours. Within the subgroup of undifferentiated sarcomas (UDS), new entities have been described based on molecular markers found through increasingly available genetic analysis in the new 2020 classification of the World Health Organization (WHO). In recent years, the importance of genetic analysis and the detection of molecular tumour markers has been growing due to the possibility of targeted therapy application and the determination of prognosis or disease course. We will present two patients with soft tissue sarcoma and neurotrophic tyrosine receptor kinase (NTRK) gene rearrangement, focusing on excellent therapeutic response to NTRK inhibitor targeted therapy with good drug tolerance.

We report our center experience in medical management of malignant childhood liver tumors Retrospective review of hospital medical data basis In the period of 19 years 13 patients were diagnosed and treated in our institution due to malignant liver tumor (8 males and 5 females). Average age at diagnosis was 4,04 years. 3 of them were born prematurely. Histopathological type of the tumor corresponded to hepatoblastoma in all cases, except one which is the case of hepatocellular carcinoma. The most frequent PRETEXT group was stage 2. Radiological imagaing and biopsy were important in making the correct diagnosis. The usual medical management consisted of neoadjuvant chemotherapy and surgical procedure followed by adjuvant chemotherapy. Overall survival is 76,9% and the average follow-up period 71,1 months. Malignant childhood liver tumors are challenging to manage necessitating multidisciplinary approach and collaboration.