Introduction: Gaucher disease (GD) and acid sphingomyelinase deficiency (ASMD) are rare lysosomal storage disorders associated with significant morbidity if left undiagnosed. Early detection through targeted screening can facilitate timely treatment and improve clinical outcomes. This study evaluated the efficacy of a selective, patient-oriented preemptive screening approach for non-neuropathic GD (nnGD) and ASMD type B (ASMD-B) in a pediatric population in Poland. Material and methods: A multicenter cohort study was conducted across 12 pediatric hematology centers between 2018 and 2023. Children aged 6-18 years with idiopathic splenomegaly and additional hematologic abnormalities underwent dried blood spottesting for beta-glucocerebrosidase and acid sphingomyelinase activity. Positive cases were confirmed using next-generation sequencing. Results: Of the 420 screened patients, 12 (2.8%) were diagnosed with GD, including 10 homozygous individuals and 2 heterozygous carriers. Three patients (0.7%) were diagnosed with ASMD-B. The estimated prevalence was 0.25 and 0.06 per 100,000 for GD and ASMD, respectively. Conclusion: Targeted preemptive screeningeffectively identified pediatric patients with nnGD and ASMD-B. These findings supportthe implementation of selective screeningstrategies in at-risk populations, enabling early diagnosis and treatmentto prevent irreversible complications.

Introduction: Due to chronic immunological disorders and immunosuppression, varicella-zoster virus (VZV) infections remain a therapeutic challenge in pediatric hematooncology (PHO) patients and children after hematopoietic stem cell transplantation (HSCT), underscoring the need for optimized preventive and therapeutic strategies. In this multicenter study, we analyzed the incidence of VZV infections and evaluated antiviral therapy outcomes in children treated in Polish PHO and transplant centers in 2012-2023. Material and methods: The study cohort comprised 13,441 patients <18 years: 11,404 (84.8%) with malignant neoplasms and 2,037 (15.2%) post-HSCT. In total, 4,607 viral infection episodes were recorded, including 167 (3.6%) VZV infections. Results: In the PHO group, 151 episodes of VZV infection occurred in 145 children. Risk of infection was over 5-fold higher in children with hematological malignancies (n = 123/5015; 2.45%) compared to those with solid tumors (n = 28/6389, 0.44%) (OR = 5.71, 95% CI 3.78-8.62, p <0.0001). The median time from malignancy diagnosis to infection was 5.91 months (IQR, 2.53-9.10). In the HSCT group, 16 episodes were recorded in 14 patients, most commonly following transplantation for ALL. The median time from HSCT to infection was 9.10 months (IQR, 3.22-11.56). In both study groups, the courses of infections were mild. Most patients received intravenous acyclovir monotherapy, with a median duration of 10 days. One child died during primary VZV infection; the remaining deaths were unrelated to VZV. Conclusions: Our findings indicate low incidence of VZV infections in Polish children with malignancy and patients after HSCT. The treatment with acyclovir showed high treatment efficacy. Rapid post-exposure prophylaxis or initiation of antiviral therapy is critical for reducingthe risk of complications and interruptions in primary disease treatment.

BACKGROUND:The increasing number of patients and better outcomes indicate the need for studying long-term time-trends of childhood cancer incidence in Poland. The aim of the study was to analyse childhood cancer incidence by sex, age and site group in Poland over 25 years between 1996 and 2020. METHODS:Data for the analysis of childhood cancer incidence were obtained from the Polish Childhood Cancer Clinical Database. The analysis of childhood cancer incidence was carried out based on the age standardized incidence rate (ASR). The ASR coefficient values were determined for five-year periods: 1996-2000, 2001-2005, 2006-2010, 2010-2015, 2016-2020. RESULTS:In the years 1996-2020, a total of 26863 new cases of cancer were registered among children and adolescents up to 17 years of age of which 21904 cases were recorded in children up to the age of 14. The most frequently diagnosed cancers were leukaemia (27·5 %), CNS tumours (19·9 %), and lymphomas (13·75 %). In most groups of cancers the disease was diagnosed more frequently in boys than in girls. The standardized incidence rate of cancers (ASR) for children up to 14 years of age in the corresponding periods was: 128·7, 148·0, 148·8, 158·7, and 167·9. INTERPRETATION:In Poland, despite fluctuations between subsequent years in the period 1996-2020, the number of new cancer cases among children up to 17 years of age was at a similar level. At the same time, the number of children aged 0-17 years in Poland in that period decreased from 10'531'160-7'672'644. Overall, we can observe an increase in the incidence of childhood cancer in Poland between 1996 and 2020 based on ASR by 23·3 %.

BACKGROUND:The prognostic role of systemic inflammation markers in pediatric soft-tissue sarcomas (STS) remains unclear. PROCEDURE:This multicenter study investigated the prognostic significance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), C-reactive protein (CRP), and lactate dehydrogenase (LDH) in 213 pediatric patients diagnosed with STS in years 2002-2023. Patients were categorized into groups: rhabdomyosarcoma (RMS, n = 126), RMS-like (n = 57), and non-RMS (n = 30). Clinicopathological data, including complete blood counts (CBCs), CRP, and LDH levels, were collected and age-adjusted. Optimal cutoffs for predicting outcomes were determined, and the prognostic value of the inflammatory markers was assessed using Kaplan-Meier survival analysis, log-rank tests, and Cox regression models. RESULTS:No significant differences in NLR, PLR, LMR, and CRP levels were observed between RMS, RMS-like, and non-RMS groups. However, LDH levels were significantly elevated in the RMS group compared with the RMS-like group. A consistent trend toward higher NLR, PLR, and CRP values was noted in patients with more advanced disease stages. Multivariate Cox regression analysis across the entire cohort identified CRP (HR 3.39, 95% CI 1.55-7.4, p = 0.002), NLR (HR 2.06, 95% CI 1.07-3.99, p = 0.03), and disease stage (HR = 0.49, 95% CI 0.26-0.95, p = 0.035) as independent prognostic factors for survival. Subgroup analyses revealed that the prognostic impact of these markers varied across histopathological subtypes, with limited utility in the RMS-like group. CONCLUSIONS:These findings highlight the prognostic value of systemic inflammatory markers in pediatric STS, emphasizing their potential to refine risk assessment and guide treatment.

PURPOSE:Soon after the Russian invasion of Ukraine in February 2022, an initiative was organized to evacuate Ukrainian children with cancer, most initially to Poland. This study assessed the impact of this rapid increase in clinical need on the Polish system of pediatric cancer care. METHODS:This multicenter longitudinal approach was performed among all 19 Polish Pediatric Oncology Centers (PPOCs). We compared PPOC capacity before the invasion with that during the first 11 weeks after the invasion, using three ratios: patients to physicians (PtP), patients to nurses (PtN), and patients to beds (PtB). In addition, we used national data from an ongoing leukemia clinical trial to assess differences between the two study periods in the time required to comply with protocol-indicated medical procedures requiring general anesthesia. RESULTS:During the study period, 237 Ukrainian refugee children with cancer were treated in PPOCs; 60% of them arrived during the first 21 days of the war. The relative increase in patients varied significantly among the PPOCs, ranging from 42% to 460%. The average PtP, PtN, and PtB ratios increased significantly by 85%, 131%, and 105%, respectively. The portion of patients experiencing a delay in obtaining medical procedures requiring general anesthesia increased from 15% before the war to 18.2% (P = .043). CONCLUSION:Because of the large number of Ukrainian children with cancer were evacuated to Poland, capacity of PPOCs was reduced, affecting cancer care for all patients. Maintaining standards of pediatric oncology care in Poland would not be possible without further patient referral to medical facilities around the world by international humanitarian collaborative action.

BACKGROUND:Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor, typically affecting infants. Kasabach-Merritt phenomenon (KMP) is a frequent and serious complication of KHE. The study aimed to analyze clinical manifestations, treatment strategies, and outcomes in children with KHE treated in Poland between 2007 and 2024. PROCEDURE:Clinical data of 42 children with KHE treated in 15 Polish pediatric hematology/oncology and surgery centers between 2007 and 2024 were analyzed retrospectively. RESULTS:KMP was present in 27/42 children (64.3%). The median age at diagnosis in children with and without KMP was 2.5 and 8 months, respectively. A male predilection was observed (61.9%), particularly in patients without KMP (13/15, 86.7%). Diagnosis of KHE required a tumor biopsy in 20 patients, including 14/15 (93.3%) of patients without KMP. Treatment strategies varied significantly between patients, institutions, and treatment periods. Systemic treatment was administered in 39 (92.9%) children, with predominating role of chemotherapy and glucocorticoids in the first period (2007-2013), and with gradually increasing importance of sirolimus in the years 2014-2018 and 2019-2024. Three children were successfully treated with surgery only. Salvage therapies ultimately controlled KHE progression/relapse in 14/17 (82.4%) patients. Only one child with metastatic, treatment-resistant cardiac KHE died of disease progression. CONCLUSIONS:Management of childhood KHE is challenging since no unified treatment recommendations exist. To optimize KHE therapy in Poland, the Section of Childhood Vascular Anomalies was established in June 2021 as part of the Polish Society of Pediatric Oncology and Hematology. Its aim is to standardize therapeutic guidelines and provide education on vascular anomalies in Poland.

Background: Acinetobacter, specifically A. baumannii, are becoming a great threat to hospitalized patients due to increasing antibiotic resistance. The aim of this study was to describe the epidemiology, clinical characteristics, antimicrobial susceptibility pattern and outcome of Acinetobacter infections in pediatric cancer patients and hematopoietic stem cell transplant (HSCT) recipients in Poland. Methods: A total of 125 episodes of Acinetobacter species infections were reported in patients <18 years treated in Polish pediatric hematology and oncology centers over a period from 2012 to 2023. Infections were subdivided into oncohematological disease (OHD) group (n = 106; 84.8%) and HSCT group (n = 19; 15.2%). Each episode represented a separate infection event; therefore, a patient who was infected more than once during the course of treatment was counted for each infection episode. Results: A. baumannii is the most common Acinetobacter species in all groups. The most common diagnoses in OHD group were acute lymphoblastic leukemia (ALL) (n = 32; 30.2%) and acute myeloid leukemia (AML) (n = 13; 12.3%). The most common underlying diseases that were indication for HSCT were hemophagocytic lymphohistiocytosis (n = 3; 15.8%) and neuroblastoma (n = 3; 15.8%). Mortality was significantly higher in the HSCT group compared to the OHD group. In the OHD group, deaths did not correlate with the type of antibiotic, with an exception for gentamicin, which correlated with higher mortality. In the HSCT group, deaths did not correlate with the type of antibiotic, except for levofloxacin that was correlated with a higher mortality rate. Conclusions: Acinetobacter infections are a great danger to immunocompromised patients. More research is needed in order to prevent and treat antibiotic-resistant bacteria.

The Childhood Acute Lymphoblastic Leukemia in Poland (cALL-POL) consortium links all pediatric oncology centers in the country and gives an opportunity to perform nation-wide clinical trials. Since there is limited data on safety and efficacy of chemotherapy replacement with blinatumomab among pediatric patients we conducted a phase 3 trial (AIEOP-BFM 2017 Poland, EudraCT # 2020-005017-41) involving children with newly diagnosed B-cell precursor ALL (BCP-ALL) who had high risk (HR) of relapse according to AIEOP-BFM criteria. Patients were randomly assigned to receive three HR blocks of chemotherapy or three sequential 28-day cycles of blinatumomab in post induction phase. The primary end points were toxicity (AESI – adverse event of special interest, AE/SAE – adverse event/serious adverse event grade ≥4) and measurable residual disease (MRD, centralized assessment by the TCR/Ig genes rearrangements) after the first and third cycle of randomization regimen. Additionally, exploratory analysis of event-free survival was performed with an event defined as a treatment resistance, relapse or death. Between June 25, 2021 and November 19, 2024, N=827 children were diagnosed with ALL in Poland. Among them N=727 (87.9%) entered the AEIOP-BFM ALL 2017 Polandclinical trial including N=638 (87.7%) with BCP-ALL. Subsequently, N=87 (female 45.6%, age at diagnosis 7.3+/-5.2 years, median follow-up 22.17 months) of BCP-ALL patients were classified as HR at the end of consolidation phase and subjected for 1:1 randomization. Among patients who completed randomized phase of trial, treatment with blinatumomab significantly reduced the risk of developing at least one clinically-relevant adverse event (AESI or AE/SAE grade ≥4)32.4% vs. 81.1%; RR(95%CI)=0.40 (0.24-0.65), p<0.0001. Moreover, the treatment with blinatumomab was superior to HR chemotherapy blocks in achieving negative MRD (97.3% vs. 56.8%; p=0.0033 RR(95%CI)=0.10(0.01-0.74) and 97.3% vs. 64.9%; p=0.053 RR(95%CI)=0.17(0.02-1.32) after the first and third block of therapy during randomization phase, respectively. Considering exploratory analysis, the MRD status after the first and third of cycle of high-risk chemotherapy or blinatumomab was a significant prognostic factor in univariate Cox regression analysis on event-free survival with HR(95%CI)=3.40(1.02-11.40) p=0.0472 and HR(95%CI)=9.90(2.85-34.33) p=0.0003, respectively. Replacing chemotherapy with blinatumomab among patients with newly diagnosed HR childhood BCP-ALL improved toxicity profile and was significantly better in reduction of MRD levels. Despite short follow-up time this resulted in improved probability of event free survival. The study was funded by the Medical Research Agency (MRA) of Poland (the cALL-POL project, ABM/2019/1).

Background/Objectives: The objective of this study was to analyze the clinical and laboratory features, management, outcomes, and complications of PRES in children with malignancies or following hematopoietic cell transplantation (HCT). Methods: This was a multicenter retrospective analysis of PRES episodes diagnosed between 2014 and 2022 in Polish pediatric hematology and oncology (PHO) centers and HCT units. The study included 438 patients treated for malignancy or post-HCT: 120 with PRES (study group) and 318 without PRES (control group). Results: PRES was diagnosed in children aged 1.7-16.5 years (median = 7.7 years). The most common underlying diagnosis was ALL (76.7%; n = 92). Symptoms of PRES included disturbances of consciousness (84.2%), seizures (80.0%), hypertension (74.2%), apathy (64.2%), abdominal pain (45.0%), visual disturbances (28.3%), and headaches (26.7%). Electrolyte abnormalities were observed in 75.0% of children, most commonly hyponatremia (49.2%) and hypokalemia (37.5%). Children with PRES were more likely to require admission to the intensive care unit (ICU) than controls (50.0% vs. 29.6%, p < 0.001). The most frequent long-term complications of PRES were hypertension (22.5%) and epilepsy (20.8%). Among PHO patients, those with PRES had significantly lower DFS (76.7% vs. 93.7%, p < 0.001) and OS (79.2% vs. 93.4%, p < 0.001). In the HCT group, PRES was also associated with lower DFS (40.0% vs. 83.3%, p = 0.012) and OS (40.0% vs. 77.8%, p = 0.047). Conclusions: PRES is a significant complication of oncological and transplant treatment in children. Its occurrence was associated with worse overall and disease-free survival. We proposed a predictive index for PRES, diagnostic criteria, and a revised name for this syndrome.

Purpose: This study aimed to identify the risk factors for acute pancreatitis (AP) and its impact on outcomes in Polish children treated for ALL. Methods: The study group included 2303 children receiving intensive chemotherapy for ALL. The group was divided into patients with at least one episode of AP and those who did not develop AP after treatment for ALL. Results: The cumulative incidence of AP in the study group was 4.08%. Older age was an independent risk factor for the development of AP (OR = 1.05; 95%CI = 1.006–1.098; p = 0.03). The overall mortality associated with AP was 2.13%. The probabilities of disease-free survival (p-DFS) and event-free survival (p-EFS) in both subgroups were 0.84 vs. 0.86, log-rank p = 0.65 and 0.75 vs. 0.80, log-rank p = 0.12, respectively. A total of 22 out of 94 patients (23.4%) with AP were re-exposed to asparaginase (ASP) during the subsequent treatment phases. Only one patient re-exposed to ASP (4.5%) developed a second episode of AP. There were no significant differences in p-DFS and p-EFS between patients re-exposed and not re-exposed to asparaginase (0.78 vs. 0.86, log-rank p = 0.27 and 0.63 vs. 0.79, log-rank p = 0.09, respectively). Conclusions: The incidence of AP in children with ALL is low and related to patients’ age. The development of AP does not seem to influence p-DFS and p-EFS in children with ALL. Recurrence of AP after re-exposure to asparaginase in patients with ALL and a history of AP is low (4.5%). Re-exposure to asparaginase after the first episode of AP does not improve either p-DFS or p-EFS in children with ALL.

IntroductionAcute lymphoblastic leukemia is characterized by a disturbed maturation of hematopoietic stem cells (HSCs) resulting in development of a malignant clone. Despite relatively positive outcome, there are still instances of disease relapse occurring due to ineffective disease eradication or primary leukemic clone alterations. Unclear significance of stem cells in the course of ALL led us to investigate and establish crucial changes in two stem cell populations - very small embryonic-like stem cells (VSELs) and HSCs during the induction phase of treatment.MethodsIn a retrospective study selected stem cells in peripheral blood and bone marrow of 60 pediatric ALL subjects and 48 healthy controls were subjected to flow cytometric analysis at 4 different time points.ResultsBoth VSELs and HSCs were elevated at the moment of ALL diagnosis compared to healthy controls, but profoundly decline until day 15. Further observations revealed an increase in HSCs with a concomitant depletion of VSELs until week 12. ALL patients with high HSCs showed positive correlation with bone marrow blasts at diagnosis. Patients with lower VSELs or HSCs at diagnosis had slightly improved response to applied therapy. We observed higher initial bone marrow lymphoblast values in patients with lower VSELs or higher HSCs in the high-risk group. The significance of VSELs in predicting treatment outcome can be illustrated by lower day 15 MRD level of patients with lower VSELs at diagnosis.DiscussionWe found HSCs and VSELs to be valid participants in pediatric ALL with possible contribution in the neoplastic process and prediction of initial treatment outcome.

Acute lymphoblastic leukemia (ALL) and glioma are some of the most common malignancies, with ALL most often affecting children and glioma affecting adult men. Proangiogenic cytokines and growth factors play an important role in the development of both of these tumors. Glioma is characterized by an extremely extensive network of blood vessels, which continues to expand mainly in the process of neoangiogenesis, the direct inducers of which are cytokines from the family of vascular endothelial growth factors, i.e., vascular endothelial growth factor (VEGF-A) and its receptor vascular endothelial growth factor receptor 2 (VEGF-R2), as well as a cytokine from the fibroblast growth factor family, fibroblast growth factor 2 (FGF-2 or bFGF). Growth factors are known primarily for their involvement in the progression and development of solid tumors, but there is evidence that local bone marrow angiogenesis and increased blood vessel density are also present in hematological malignancies, including leukemias. The aim of this study was to examine changes in the concentrations of VEGF-A, VEGF-R2, and FGF-2 (with a molecular weight of 17 kDa) in a group of patients divided into specific grades of malignancy (glioma) and a control group; changes of VEGF-A and FGF-2 concentrations in childhood acute lymphoblastic leukemia and a control group; and to determine correlations between the individual proteins as well as the influence of the patient’s age, diet, and other conditions that may place the patient in the risk group. During the statistical analysis, significant differences in concentrations were found between the patient and control groups in samples from people with diagnosed glioma and from children with acute lymphoblastic leukemia, but in general, there are no significant differences in the concentrations of VEGF-A, VEGF-R2, and FGF-2 between different grades of glioma malignancy. Among individuals treated for glioma, there was no significant impact from the patient’s gender and age, consumption of food from plastic packaging, frequency of eating vegetables and fruit, smoking of tobacco products, the intensity of physical exercise, or the general condition of the body (Karnofsky score) on the concentrations of the determined cytokines and receptor. The listed factors do not bring about an actual increase in the risk of developing brain glioma.

Introduction : Approximately 10% of pediatric patients with malignancies carry germline predisposing variants. Regarding pediatric patients who developed lymphoma, the pathogenic abnormalities frequently affect DNA repair genes. Identifying these aberrations may contribute to tailored clinical management, appropriate screening protocols, management of comorbidities, and genetic counseling. Therefore, we aimed to identify genetic predispositions to pediatric lymphoma based on familial history and phenotypical features. Methods: We obtained clinical information about 75 patients diagnosed with lymphomas from 61 families, who met ≥1 following inclusion criteria: C1. positive familial history of cancer, C2. specific histopathological types of lymphoma, C3. multiple malignancies, C4. congenital abnormalities or specific dysfunctions, and C5. excessive toxicity of oncological treatment. Patients with known genetic diagnoses or those without consent were excluded from our study. To date, 42 families (69%), encompassing 54 patients, have been tested using next-generation sequencing (NGS): targeted panels were employed in cases with a strong clinical suspicion of a specific syndrome, while whole exome sequencing was performed in other cases. Variants were filtered based on a list of genes involved in cancer development or/in immune dysregulation using the following filters: 1) frequency below 5%; 2) at least 7 reads, 3) positive verification in Integrative Genomics Viewer. Their pathogenicity was estimated based on American College of Medical Genetics guidelines. Selected variants were then directly sequenced using Sanger methods in patients and their available relatives. Results:Among 75 lymphoma patients (49 males, 75%) with a median age of 8.5 years (IQR: 5-13), the most commonly observed tumors included: Hodgkin lymphoma (HL; 27 patients, 36%), T-cell lymphoblastic lymphoma (T-LBL; 14 patients, 19%), and diffuse large B-cell lymphoma (DLBCL; 10 patients, 13%). The most common inclusion criteria were specific histopathological types of lymphoma, which were present in 33 (54%) families, followed by C1. (19, 31% families), C4. (19, 31% families), C3. (17, 28% families), and C5. (8, 13% families). Among C1. families, 13 cases (68%) involved both parent and child(ren), and 3 cases (16%) involved only siblings. C2. families included primarily T-LBL (10, 30% families), DLBCL (9, 27% families), and primary mediastinal B-cell lymphoma (PMBL; 6, 18% families). C3. families had leukemias in 5 (29%), central nervous system tumors in 4 (24%), and >1 lymphoma in 2 (12%) cases. C4. criterion was met due to immunodeficiency in 7 patients (37%) and polyposis in 4 patients (21%). Notably, among the 7 patients (88%) with excessive toxicities, specific types of lymphoma, mainly T-LBL, were observed. Pathogenic, causative variants, were found in 10 families (24% of tested), the variants were particularly located in CMMRD-related genes (4 families). There were also single patients carrying pathogenic: 1) TP53 variant (NM_000546:c.155_164delAATGGTTCAC), 2) compound heterozygous ATM aberrations (NM_000051:c.434T>G & large deletion of ex40-64), 3) BLM biallelic variants (NM_000057:c.1642C>T & c.2833G>A), 4) CXCR4 defect (NM_003467:c.1012dup; het), 5) FANCM biallelic variants (NM_020937:c.1972C>T; het), and 6) CHEK2 splice-site mutation (NM_001005735:c.573+1G>A; het) In the remaining 22 families, we found variants that may possibly contribute to lymphoma development, e.g. two patients with monoallelic pathogenic variant within the BRCA1 gene (NM_007300:c.4035delA and c.3756_3759del, both het) or patient with HL and Ewing's sarcoma, with concomitant PALB2 (NM_024675.1:c.110G>A; het); and DDX41 mutation (NM_016222:c.299-3C>T). From this group gene variant involving: LCK (NM_005356:c.1176C>G; p.Asn392Lys, het) and NTRK3 (NM_001012338:c.1745G>A; p.Arg582Gln, het) were selected as the most promising candidates for further functional tests. Conlcusion: The implementation of the NGS approach enables the uncovering of genetic predispositions to lymphoid malignancies, particularly in patients selected based on specific clinical criteria. Germline aberrations in DNA repair genes are the most frequently found in children diagnosed with lymphomas but also, several rare aberrations affecting cancer-related genes were identified.