The COVID-19 pandemic was a major driver for the integration of telemedicine in many different medical fields, but applications in pediatric oncology in Germany remain scarce. This study evaluated the perceptions of benefits and limitations of telemedicine among pediatric oncology patients and their families during intensive cancer treatment prior to its implementation. A cross-sectional questionnaire survey was conducted at the University Hospital Schleswig-Holstein, Campus Kiel, between February and April 2021 during the COVID-19 lockdown, with responses from 119 participants. Factors such as travel time, time at home, COVID-19 exposure, and potential impacts on diagnostics and psychosocial support were assessed. Overall, telemedicine was viewed favorably, with advantages rated higher than disadvantages by both caregivers and patients (mean score 3.79 vs. 3.36, p < 0.01). Key benefits included reduced travel and waiting times, more time at home, and lower COVID-19 exposure, each with mean scores above 4. Reported disadvantages were the lack of on-site physical examinations, absence of blood testing, and reduced social interaction with hospital staff, other patients, and their families. These findings suggest generally positive perceptions of telemedicine in pediatric oncology care, and indicate that a hybrid model combining remote and in-person visits could potentially address diagnostic and social needs in this vulnerable patient group.
Bright IDEAS is a problem-solving skills intervention designed to aid caregivers of children with cancer. While this paradigm has been well-studied in high-income settings, the feasibility and utility of this intervention in low-resource settings has been largely unexplored. This pilot study examined whether Bright IDEAS was perceived as workable, usable, and useful by professionals in Uganda caring for patients and caregivers within pediatric oncology settings. A single-arm pilot feasibility study design was utilized in this study. Participants included 24 Ugandan health and psychosocial professionals trained in the Bright IDEAS model. Quantitative data was obtained from 14 participants, using a post-training survey of usability, feasibility, comfort, practicality, and perceived utility on a 5-point Likert scale (1 = Poor to 5 = Excellent). Open-ended items assessed barriers, enablers, and experiences of implementation. Descriptive statistics and thematic content analysis were conducted. Respondents rated both overall feasibility and usability highly (M = 4.3, SD = 0.6). They reported comfort in teaching caregivers about the intervention (M = 4.1) and reported Bright IDEAS strategies were easy for caregivers to understand (M = 4.4). The major qualitative themes were perceived empowerment of caregivers, strengthened problem-solving skills, and enhanced therapeutic engagement. Relevant challenges included lack of support from institutions, time constraints, and inadequate resources. Bright IDEAS was widely believed to be valuable for Ugandan professionals and the study demonstrated strong perceived impact on caregiver coping and communication. These results support additional contextual refinement and robust testing of Bright IDEAS in Ugandan oncology and psychosocial care contexts.
High tumor mutational burden (TMB-H), defined as ≥10 non-driver somatic mutations per mega base of genome sequenced (mut/Mb), and high microsatellite instability (MSI-H), which can lead to TMB-H, are both associated with response to the immunotherapy pembrolizumab. Data from the KEYNOTE-158 study demonstrated that the association between TMB-H and response to pembrolizumab is independent of MSI-H status. Because data in children are limited, the prevalence of TMB-H in pediatric solid tumors is unclear. This study sought to examine TMB-H prevalence across solid tumor types that are most common among pediatric tumors using real-world data. This retrospective, cross-sectional study included data from FoundationCORE® solid tumor biopsies that were sequenced by comprehensive genomic profiling between 2013 and 2023. All patients were <18 years of age at the time of specimen collection. TMB-H prevalence was assessed among patients with non-MSI-H tumors (including those with MSI-low and microsatellite-stable tumors) and by key patient demographics and disease characteristics. Among 3533 patients with non-MSI-H solid tumors, TMB-H prevalence was 1.42% and was significantly higher in children aged 12-17 years than in children aged <12 years (2.17% vs 0.98%; p = 0.006). There were no significant differences based on sex, genomic ancestry, tissue of origin, disease stage at testing, or whether the tissue sample was from a metastatic versus nonmetastatic site. Prevalence varied by tumor type but was <3% across subgroups, including glioma, central nervous system non-glioma, and peripheral nervous system tumors. Overall, TMB-H prevalence was low across solid tumor types that are frequently observed in children.
Childhood cancer represents an increasingly recognized priority in global health, with the World Health Organization's Global Initiative for Childhood Cancer aiming to achieve 60% survival for six index cancers by 2030. In Nigeria, leukemia and lymphoma constitute a substantial proportion of pediatric malignancies, yet outcomes remain dramatically poorer than in high-income countries. This review examines the current state of childhood leukemia and lymphoma in Nigeria, synthesizing available epidemiological data, discussing unique biological features, and analyzing the multifactorial challenges that perpetuate poor survival. Treatment abandonment exceeds 37%, mortality approaches 32%, and critical infrastructure gaps-including limited radiotherapy access, absence of bone marrow transplantation, and inadequate diagnostic capacity-compound the problem. The WHO's interventions through the Global Initiative and technical support for registry development offer frameworks for progress. Future perspectives emphasize the necessity of population-based cancer registries, expanded health insurance coverage, investment in regional diagnostic and treatment centers, and sustainable financing mechanisms to bridge the survival gap.
Rhabdomyosarcoma is the third most common extracranial solid tumor of childhood. Despite extensive research over the preceding decades, prognosis in children with metastatic or recurrent disease remains very poor with overall 5-year survival rates under 20%. Liquid biopsy is emerging as an effective, clinically applicable, noninvasive adjunct to conventional oncological management. To date, liquid biopsy has predominantly been applied in the field of adult oncology. Translation into pediatric malignancies, including rhabdomyosarcoma, remains at an early stage with small cohort studies addressing feasibility and technique optimization. This narrative review addresses the current literature in the field of liquid biopsies in rhabdomyosarcoma considering a variety of circulating biomarkers including ctDNA, mRNA, miRNA, proteins, and tumor cells. Liquid biopsies have the potential to revolutionize real-time tumor monitoring and personalized oncological treatment. The results of further large-scale prospective clinical trials in rhabdomyosarcoma are necessary to enable successful integration into standard clinical care.
Marathe et al. report encouraging results from a step-down pathway for low-risk fever and neutropenia in pediatric and adolescent-young adult oncology patients, with reduced hospitalization and no sepsis or infection-related mortality. Their work is an important contribution to risk-adapted supportive care. This Article Commentary argues, however, that early discharge is not a universally portable intervention. Its safety depends not only on patient biology and initial clinical stability, but also on the surrounding health-care infrastructure: rapid microbiology, timely antibiotics, 24-h oncology consultation, reliable transport, informed caregivers, and guaranteed urgent reassessment. From the perspective of pediatric hematology-oncology practice in Van, eastern Türkiye, the distance from tertiary care, variability in after-hours pediatric oncology expertise, and uneven access to rapid reassessment can make direct adoption of such a pathway nearly impossible without explicit safeguards. The central issue is therefore not whether low-risk patients can ever be discharged early, but which patients, families, centers, and regional systems can do so safely. Future studies and guidelines should define an auditable infrastructure threshold and report implementation outcomes alongside clinical outcomes, so that early-discharge pathways reduce hospitalization without shifting avoidable risk onto families and geographically remote services. This distinction is essential for equitable implementation in real-world oncology practice.
Viridans group streptococci (VGS) are an important cause of bacteremia inpediatric oncology patients and hematopoietic stem cell transplantation (HSCT) recipients, with the potential to viridans streptococcal shock syndrome (VSSS). Increasing β-lactam resistance has raised concerns about the adequacy of current empiric treatment strategies, which typically avoid routine glycopeptide use. We retrospectively analyzed 53 episodes of VGS bacteremia (VGSB) in 42 pediatric and adolescent patients who underwent chemotherapy or HSCT at Kobe Children's Hospital from May 2016 to August 2024. Clinical characteristics, antimicrobial susceptibility, inflammatory markers, and recurrence patterns were assessed. Acute myeloid leukemia (AML) accounted for 49% of episodes, and 60% occurred during cytarabine-containing chemotherapy. Seven patients experienced repeated episodes of VGSB-all with AML; among them, five developed cefepime resistance, and three showed a transition from susceptible to intermediate or resistant isolates during subsequent episodes. Cefepime susceptibility was 64%, whereas all isolates remained susceptible to vancomycin. Exposure to prophylactic antibiotics was significantly associated with the isolation of cefepime-intermediate or resistant strains (10/19 vs. 9/36, p = 0.03). Routine glycopeptide prophylaxis is not justified; however, our findings suggest that AML patients with recurrent VGSB or prior cefepime-nonsusceptible VGS may represent a high-risk subgroup for cefepime-nonsusceptible VGS infection. Further studies are needed to validate risk-adapted antimicrobial strategies in this population.
In childhood, cancer survivors are at a higher risk of developing secondary cancers, including human papillomavirus (HPV)-related malignancies, compared with the general population. In Turkey, HPV vaccines are not included in the National Immunization Program (NIP). This study assessed the knowledge, awareness of HPV, and the willingness for HPV vaccines among survivors of childhood hematologic malignancies and their parents. This cross-sectional study was conducted with 156 parents and their children (age 9-18 years), in accordance with the sample size calculation. A structured questionnaire prepared for both parents (19 questions) and children (15 questions) was employed for data collection, and the data were gathered through face-to-face interviews or by phone. Regarding the questions evaluating knowledge of HPV, 34% of the parents and 29.5% of the children participating in the study had heard of HPV and the HPV vaccine. The most important sources of information for parents were physicians (43.4%) and television (26.4%), while for children it was social media (52.7%) and physicians (21.7%). HPV vaccination rates were very low in both parents and children (3.2% and 2.6%, respectively). The most common reasons for not receiving the vaccine were the lack of a physician's recommendation and insufficient information in both groups. Logistic regression analysis evaluating factors associated with HPV awareness revealed that high educational level (OR: 2.85 [95% CI: 1.22-6.61]; p = 0.011), receipt of privately administered vaccines (not including in NIP) (OR: 2.45 [95% CI: 1.35-4.45]; p = 0.004, and female sex (OR: 1.97 [95% CI: 1.19-3.26], p = 0.007) were significant predictors. Raising awareness about HPV vaccines is essential to improve immunization coverage especially in survivors of hematologic cancers. Efforts are required to strengthen the training of different departments and encourage their collaboration and increase vaccination rates.
Bone marrow failure syndromes (BMFS) encompass a spectrum of acquired and constitutional disorders characterized by impaired hematopoiesis and cytopenias. In pediatric patients, constitutional BMFS represent up to 50% of cases, yet their diagnosis remains challenging due to subtle or absent extra-hematologic manifestations that mimic immune aplastic anemia. Accurate differentiation is essential, as it directly influences prognosis, therapeutic strategy, surveillance for extra-hematopoietic complications, and donor selection for hematopoietic cell transplantation. This review presents a structured diagnostic framework for pediatric BMFS, integrating clinical history, physical examination, bone marrow morphology, flow cytometry, cytogenetic analysis, disease-specific functional assays, and next-generation sequencing (NGS). Chromosomal breakage testing remains the gold-standard assay for Fanconi anemia, while telomere length measurement is the strongest predictor for differentiating constitutional from immune BMF. NGS enables comprehensive germline variant detection, resolves diagnostically ambiguous presentations, and informs genotype-guided familial screening. Recognition of disease-specific patterns of clonal hematopoiesis further refines diagnostic precision and risk stratification. A stepwise, evidence-based approach is essential to optimize early diagnosis and long-term outcomes in pediatric patients with BMFS.
Imatinib in children with chronic myeloid leukemia (CML) is associated with growth deceleration. However, the long-term impact on final height remains less clear. The aim was to evaluate the effect of prolonged imatinib on linear growth at skeletal maturity. A cross-sectional study was conducted at a single center (2020-2021). Patients with chronic-phase CML on imatinib, diagnosed before 13 years and who had attained skeletal maturity at enrollment, were included. Anthropometry, sexual maturity rating, bone age, and evaluation for causes of short stature were performed. Longitudinal height data were retrieved from clinic records and compared with population-specific growth charts. Of 46 screened patients, 13 fulfilled the inclusion criteria. Mean age at diagnosis and enrollment was 9.3 ± 2.3 and 23.7 ± 2.6 years. The median duration of imatinib therapy was 14.3 years (IQR: 14.2-16), with 184.4 patient-years of follow-up. Mean height z-score declined from -0.6 ± 1.2 at diagnosis to -1.1 ± 0.9 at maturity (p = 0.04). In those administered imatinib before the onset of pubertal growth spurt, the decline was significant (-0.5 ± 0.6 to -1.3 ± 0.6, p = 0.03), compared to those administered after the pubertal growth spurt (p = 0.60). In one of the longest follow-up cohorts of children with CML reported to date, imatinib resulted in growth deceleration, particularly when initiated before the onset of pubertal growth spurt. Despite catch-up growth during adolescence, final height z-scores remained reduced at skeletal maturity.
This study explored protein expression in B-cell acute lymphoblastic leukemia (B-ALL) patients with and without elevated weight or obesity and controls to understand global proteomic differences between newly diagnosed B-ALL patients and controls as well as the influences of elevated body mass index (BMI) on pretreatment inflammatory and immune-related protein expression in B-ALL patients. Protein expression was measured in serum samples of pediatric patients (aged 1-21 years) with newly diagnosed B-ALL (n = 39), and age and sex-matched controls (n = 41) using OLink panels. We examined normalized protein expression data clustered by patient information in -unsupervised hierarchical clustering and principal component analysis. Of 239 assays, 128 assays differed significantly based on B-ALL diagnosis and 4 assays (APLP1, CDHR5, GHRL, SEZ6L) varied significantly as a function of BMI. In healthy individuals, oncology marker furin (p.adjust = 0.016) was more highly expressed in the high-BMI category; this trend was reversed for B-ALL individuals. Furin expression is often upregulated in malignancies and obesity; however this suggests its expression may follow unique patterns in pediatric B- ALL patients with elevated BMI.
The 6-min cycling test (6MCT), a submaximal endurance test, has not yet been applied in pediatric oncology. This study evaluates its feasibility and validity in 71 childhood cancer patients (9.6 ± 4.0 years). For validation, 46 patients additionally underwent cardiopulmonary exercise testing (CPET). Performance in the 6MCT (total revolutions) was correlated with peak oxygen uptake (VO2peak) and peak work rate (WRpeak) using Spearman's correlation. Linear regressions assessed the predictive value of VO2peak and WRpeak on 6MCT performance. Sixty-six participants (93%) successfully completed the 6MCT, averaging 550 ± 129 revolutions. Revolutions correlated moderately with VO2peak (ρ = 0.46, p = 0.001) and strongly with WRpeak (ρ = 0.64, p < 0.001). VO2peak significantly predicted 6MCT performance (p = 0.001, R2 = 0.214), whereas WRpeak explained more variance (p < 0.001, R2 = 0.488). The results demonstrate that the 6MCT is a feasible, valid endurance assessment in this population, offering a promising alternative when gold standard testing is not available.
Monitoring donor-recipient chimerism following hematopoietic stem cell transplantation (HSCT) is essential for assessing engraftment success, early identification of graft failure and relapse, and guiding immunomodulating interventions. Recent advancements in molecular technologies, particularly digital droplet PCR (ddPCR) and next-generation sequencing (NGS), have markedly improved the sensitivity and precision of chimerism detection, allowing the identification of recipient cells at levels below 0.1%. These advancements enable more accurate and dynamic monitoring compared to traditional methods, which are limited in terms of sensitivity and specificity. In pediatric patients, the interpretation of chimerism results is complicated by unique factors, including thymic recovery, exposure to serotherapy agents such as ATG or alemtuzumab, and constraints related to small blood volume. These factors affect the kinetics of donor cell engraftment and the dynamics of mixed chimerism in different hematopoietic lineages. This review presents the current understanding of the biological basis of chimerism, compares traditional and advanced detection methodologies, and details lineage-specific chimerism kinetics in children. It also provides practical guidance for interpreting serial chimerism data to inform timely and preemptive clinical interventions. Owing to the limited pediatric-specific data, adult findings were integrated where appropriate, underscoring the urgent need for pediatric validation, assay harmonization, and standardized implementation protocols to optimize transplant outcomes in children.
Hematopoietic stem cell transplantation (HSCT) has greatly improved the survival of children with leukemia; however, long-term adverse effects remain a concern. This study aims to compare the effects of total body irradiation (TBI)-based and chemotherapy-based conditioning regimens on insulin resistance in children undergoing HSCT. Patients under 18 who underwent HSCT between April 2010 and October 2023 were evaluated. Seventy-six patients (M/F:48/28) with leukemia were included in this prospective descriptive cross-sectional study. Clinical and laboratory data, including oral glucose tolerance test (OGTT), were collected. The TBI group consisted of 45 patients with ALL (66.1%), and the non-TBI group consisted of 31 patients, including 23 with ALL and 8 with AML. The median time from HSCT to OGTT was 2.7 years (IQR, 1.8-3.8) and did not differ between the two groups. Body mass index and serum lipids, except HDL cholesterol, did not differ between the TBI and non-TBI groups. Twelve patients (26.6%) in the TBI group and 6 patients (19.3%) in the non-TBI group had impaired OGTT results (p > 0.05). All four obese patients had normal glucose tolerance. The TBI group had significantly higher peak and total insulin levels during the OGTT than the non-TBI group (p = 0.02, p = 0.02, respectively). Although HbA1c and HOMA-IR did not differ between the two groups, the Insulin Sensitivity Index (ISI) was significantly lower in the TBI group, indicating reduced peripheral insulin sensitivity (p = 0.04). TBI is a risk factor for reduced insulin sensitivity in pediatric HSCT survivors, which is a risk for type 2 diabetes and cardiovascular disease without leading to obesity.
Neuroblastoma (NBL) constitutes the most common extracranial solid tumor in children that arises from the sympathetic ganglia. Its manifestations depend on the localization of the tumor and metastases. This research aimed to assess the incidence of ophthalmological symptoms and their correlations with different prognostic factors. We collected and analyzed retrospectively the data of 776 children with a clinical diagnosis of peripheral neuroblastic tumors reported between 2004 and 2022 from 14 Polish pediatric oncology centers. Ophthalmological symptoms occurred in 17.10% of the patients, and in 12.70% they were diagnosed at the time of the first presentation. The reported manifestations comprised opsoclonus-myoclonus syndrome (OMS), Horner syndrome (HS), exophthalmos, periorbital hemorrhages, with the highest incidence of OMS (4.74% of all the patients). Moreover, we described the cases with neurological manifestations of NBL like paraparesis and facial nerve paresis. The age correlated with the form of symptoms, and HS was observed in the youngest patients. Similarly, the time from the symptoms onset to NBL diagnosis differed significantly among the patients, therefore the diagnosis of HS was associated with the longest period. In conclusion, the ophthalmological manifestations of NBL represent an essential group of symptoms. Therefore, clinicians should consider them as possible signs of tumors, particularly HS, which may be most challenging in the diagnostic process.
In the treatment of hemophagocytic lymphohistiocytosis (HLH), the effectiveness of ruxolitinib has been reported internationally. However, in Japan, ruxolitinib use has been limited due to its off-label status. We conducted a nationwide, multicenter, retrospective survey in Japan on the use of ruxolitinib in pediatric HLH. Seventeen patients from nine institutions were included: primary HLH (n = 5), Epstein-Barr virus-associated HLH (EBV-HLH; n = 3), and post-transplant HLH (PT-HLH; n = 9). Ruxolitinib was used for refractory disease (n = 14) as well as for maintenance therapy in primary HLH/EBV-HLH (n = 3). In most patients, ruxolitinib was employed in combination with conventional therapies. Among refractory cases, the overall response rate was 80% for primary HLH/EBV-HLH and 89% for PT-HLH. The three patients who received ruxolitinib as maintenance therapy achieved sustained remission: two remained in remission until subsequent transplantation, and one did not require transplantation. Considering the results, we propose that ruxolitinib is a promising therapeutic option for pediatric HLH.
The complexity of sickle cell disease (SCD) goes beyond hematological manifestations, affecting different organs and systems, including auditory system. We aimed to assess Central Auditory Processing (CAP) abilities in children with SCD as well as to detect risk factors for Auditory Processing Disorders (APD) in children with SCD. A diagnostic observational cross sectional study that included thirty-three patients aged 6-16 years with a confirmed diagnosis of SCD. Demographic, clinical and laboratory characteristics were collected. Audiological testing included tympanometry, pure tone audiometry, IQ testing, specific history for CAP abilities and APD screening test battery. Among the 33 screened patients, all had normal pure tone audiometry, and 2 patients had middle ear affection. Auditory Perception was assessed in 25 eligible participants. The majority of the studied patients (n = 21, 84%) APD. The most affected tests were patterning (n = 21, 84%) and auditory memory (n = 16, 64%). Results showed positive correlation between age of transfusion and dichotic listening, APD was commonly encountered in children with SCD, thus screening for APD is recommended in all patients with SCD for early detection and intervention of any abnormalities.
Idiopathic pneumonia syndrome (IPS) is a serious complication following allogeneic hematopoietic cell transplantation (HCT), often treated with methylprednisolone (mPSL) pulse therapy. However, treatment responses vary. This study aimed to identify predictors of poor response to mPSL monotherapy. Among 289 patients who underwent allogeneic HCT, 25 developed IPS and received mPSL pulse therapy. Clinical responses were categorized as complete (CCR), partial (PCR), or no response (NR), based on oxygen requirements within 28 days. We compared baseline characteristics of responders (CCR: n = 5; PCR: n = 6) and non-responders (NR: n = 14). Univariate analysis revealed that IPS onset on day +73 or later (p = 0.033), reduced intensity conditioning (p = 0.033), use of total body irradiation (p = 0.049) or fludarabine (p = 0.042), and nonuse of busulfan (p = 0.049) in preparative regimens were associated with poor response. Multivariate analysis identified a longer time from transplantation to IPS onset as a significant predictor of poor response (Odds Ratio 1.017 per 1-day increase; 95% CI 1.007-1.036; p = 0.045). The present study may provide valuable insights into how the responsiveness to mPSL varies depending on the time of IPS onset. Alternative therapeutic strategies may be needed for patients with late-onset IPS.
Pediatric Hodgkin lymphoma (HL) treatment has increasingly shifted toward response-adapted protocols, aiming to minimize radiotherapy and employ intensive chemotherapy such as OEPA/COPDAC. We retrospectively reviewed treatment outcomes and toxicities in pediatric HL patients treated with OEPA/COPDAC between 2015 and 2019 at a tertiary care center in Pakistan, a resource limited country, following the Euronet PHL-C1 protocol with radiotherapy reserved for inadequate interim responses. Clinical features, treatment-related toxicities, and hospital admissions were documented. The cohort included 20 patients with a median age of 12 years; 13 (65%) achieved complete remission after OEPA induction and avoided radiotherapy. Toxicities were frequent-15 (75%) after OEPA-1 and 13 (68%) after OEPA-2-most commonly gastrointestinal symptoms and febrile neutropenia. Hospitalization was required in 9 (45%) after the first cycle and 11 (58%) after the second, with one treatment-related death from febrile neutropenia. At median follow-up, overall survival was 95% (95% CI: 69.47-99.28%) and event-free survival was 85% (95% CI: 60.38-94.90%). These findings highlight that OEPA/COPDAC achieves high survival rates even in advanced-stage pediatric HL within low-resource settings. However, the substantial toxicity burden and frequent hospitalizations underscore the need for enhanced supportive care and further evaluation in larger, long-term studies.
