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 patients with progressive and refractory solid tumors face a challenging prognosis. Despite advancements in treatments like immunotherapy and targeted therapy, survival rates remain low for certain tumor types. Decision-making in these complex cases often necessitates a multidisciplinary approach, integrating risk-based management, precision medicine, and access to clinical trials. Artificial intelligence (AI) technologies, particularly large language models (LLMs), hold promise for improving clinical reasoning and decision support in pediatric oncology. This study evaluated the decision-making capabilities of five AI tools—ChatGPT, Gemini, Claude, Perplexity, and OpenEvidence—in six hypothetical cases of refractory or progressive pediatric solid tumors. Each AI tool was presented with two sequential queries: a request to generate potential treatment options and then a request to identify and justify the most appropriate option from its initial list. The AI tools generated a total of 124 treatment recommendations, with an average of 24.8 per tool. Clinical trial enrollment was the most frequently selected “best option,” accounting for 55.2% of cases. Other notable recommendations included targeted therapy (17.2%), surgery (10.3%), chemotherapy (10.3%), best supportive care (10.3%), and immunotherapy (3.4%). Notably, the AI tools exhibited distinct tendencies in their decision-making approaches, with some favoring aggressive interventions and others emphasizing supportive or palliative care. AI tools demonstrate potential for assisting with complex treatment decisions in pediatric oncology, particularly by identifying clinical trial options. However, the observed variability in recommendations underscores the need for careful human oversight to ensure that AI-generated suggestions align with clinical evidence, patient and family preferences, and the overall goals of care. Future research should explore how AI tools can be further refined to incorporate nuanced patient-specific information and address the emotional and psychological impact of AI-assisted decision-making.

Hypoalbuminemia and cancer cachexia predict poor survival in adult cancers, with limited studies in pediatrics. Also, the serial recovery kinetics of serum albumin and its effect on cancer outcomes are unknown. This study investigated trends and determinants of serum-albumin at various time points of therapy and their influence on 3-year survival of pediatric cancers. It included cancer patients below 18yrs. Baseline systemic symptoms, stage/risk-group, nutritional status and serum-albumin at baseline, 3-months, 6-months and 12-months were recorded from hospital database along with outcomes like relapse/death and toxicity. Among 402 patients, hemato-lymphoid cancers (57.71%)were more common. Prevalence of hypoalbuminemia at baseline, 3 m, and 6 m was 46.52%, 26.45% and 22.0%, respectively. Patients with hypoalbuminemia at baseline (HR = 2.1; p = 0.000), 3 m (HR = 2.28; p = 0.000), or 6 m (HR = 2.02; p = 0.001) had lower overall-survival (OS) in univariate analysis, while on multivariate analysis, only risk group (HR = 1.74; p = 0.009) and 6 m albumin (HR = 3.33; p = 0.001) independently predicted OS. For event-free-survival (EFS) risk-group (HR = 1.59; p = 0.018) and 6 m-albumin (HR = 2.91; p = 0.001) were the only independent predictors. Out of various predictors of serum albumin, systemic-symptoms (OR = 8.01, p = 0.008) and baseline-malnutrition (OR = 2.08; p = 0.004) independently predicted baseline-hypoalbuminemia. Organomegaly measured as liver/spleen size(r=-0.39) and systemic inflammation measured as serum-globulin (r=-0.37) had negative correlation with baseline-albumin. In contrast, 6-month albumin was dependent only on baseline systemic symptoms (OR = 5.28; p = 0.007) and independent of baseline malnutrition (OR = 1.72; p = 0.091). We conclude that while baseline albumin is influenced by multiple factors, such as malnutrition, systemic symptoms, inflammatory state (hypergammaglobulinemia), and disease bulk (organomegaly), 6-month albumin is independent of baseline malnutrition and serves as a better predictor of the cancer-inflammation-cachexia-cascade and ultimate survival.

We retrospectively analyzed the clinical outcomes of seven patients receiving palliative treatment with oraltemozolomide (TMZ)/etoposide (ETP) for recurrent or progressive neuroblastoma (NB). Patients received a median of three cycles of TMZ/ETP. One patient achieved complete response (CR), three showed stable disease, and three showed progressive disease. The median time to progression in the six patients without achieving CR was 82 days excluding one achieving CR for >222 days. Grade 3 hematological toxicities were common but manageable, and no patients experienced severe non-hematological toxicity. TMZ/ETP is a feasible palliative chemotherapy option for certain patients with recurrent or progressive NB.

Late effects are a major concern after pediatric hematopoietic stem cell transplantation (HSCT), but data on health outcomes beyond early adulthood remain scarce. This study assessed long-term morbidity and mortality in one of the earliest childhood cancer cohorts treated with HSCT. The study comprised 52 male childhood cancer survivors (survival ≥5 years), treated with HSCT in 1983–2001 at a median age of 6.1 years, and 257 matched population controls. Finnish national healthcare registries provided data on prescription drug purchases, reimbursements for chronic diseases, hospitalizations, and late mortality. Median follow-up was 24.9 years. Compared to population controls, survivors had increased risk for diabetes (HR 16.4, 95% CI 4.33–61.8), severe hypertension (HR 11.4, 95% CI 3.42–37.8), purchases of lipid-lowering drugs (OR 13.5, 95% CI 4.87–41.3), and purchases of antihypertensives (OR 2.58, 95% CI 1.28–5.12). HSCT survivors had also higher risk for hospitalizations due to cardiovascular diseases (HR 6.13, 95% CI 1.52–24.7) and neurological conditions (HR 4.79, 95% CI 1.73–13.2). New diagnoses of epilepsy and secondary neoplasms emerged beyond 20 years post-transplantation. Chronic graft-versus-host disease was associated with increased purchases of thyroxine, growth hormone, and lipid-lowering drugs. Given the high risk for diabetes, hypertension, and dyslipidemia, proactive cardiovascular risk assessment is essential in long-term care after pediatric HSCT. The occurrence of late-onset complications underscores the importance of structured lifelong follow-up.

The overall incidence of core binding factor acute myeloid leukemia (CBF-AML) in pediatric patients has been reported to be 19%–44.3%. However, the prognostic role of KIT mutations in pediatric CBF-AML remains controversial. This study aimed to investigate whether incorporating KIT mutation status into risk stratification improves long-term outcomes. A total of 114 pediatric CBF-AML patients treated under BCH-AML 2005 protocol and CCLG-AML 2015 protocol were enrolled. KIT mutations were identified using Sanger sequencing, classified as high-risk in CCLG-AML 2015. Relationships between clinical and biological features, outcomes and KIT mutations were evaluated across genetic subgroups. KIT mutations were identified in 25.4% pediatric CBF-AML, with comparable mutation rates in RUNX1::RUNX1T1 and CBFβ::MYH11 subgroups. Patients with KIT mutations showed higher leukemia burdens, including increased bone marrow blasts and white blood cell (WBC) indices. RUNX1::RUNX1T1 subgroup showed poorer 5-year OS than CBFβ::MYH11. Patients with KIT mut17+ exhibited significantly lower OS, EFS compared to those with KIT mut8+ and KIT wt. Notably, RUNX1::RUNX1T1+KIT mut17 + patients exhibited significantly worse OS among genetic subgroups but achieved improved OS under CCLG-AML 2015. KIT exon 17 mutational status and treatment protocol was identified as independent prognostic factors for OS and EFS in CBF-AML and RUNX1::RUNX1T1-AML. Our study found that prospective evaluation of KIT mutations is crucial in pediatric CBF-AML, particularly in RUNX1::RUNX1T1 patients, where the survival can be significantly improved by high-risk chemotherapy and hematopoietic stem cell transplantation.

Sickle cell anemia (SCA) is associated with a high prevalence of cerebrovascular complications, such as ischemic stroke, particularly at young ages. Among various molecules, vitamin D has been implicated in stroke occurrence. By binding to the vitamin D receptor (VDR), vitamin D regulates several mechanisms, potentially influencing pathways involved in the pathophysiology of cerebral vasculopathy. Here, we evaluated the association between VDR gene polymorphisms and 25-hydroxyvitamin D (25(OH)D) levels with CVD in a cohort of patients with SCA. The frequency of CVD and laboratory data were retrospectively obtained from the medical records. Genotyping for the functional FokI (rs2228570) and Cdx-2 (rs11568820) VDR polymorphisms was performed in 459 unrelated SCA patients. 25(OH)D levels were measured in a subset of 45 patients. The TT genotype of the FokI VDR polymorphism was associated with a higher frequency (OR: 2.82; 95% CI: 1.38–5.76, p = 0.006) and higher cumulative incidence (34% vs 16%, p = 0.001) of CVD compared to the other genotypes. Among patients under hydroxyurea (HU) therapy, individuals with the TT-FokI genotype (median: 13.9 ng/mL) had lower 25(OH)D levels compared to those with CC/CT genotypes (median: 20.2 ng/mL; p = 0.033). Similarly, patients with CVD and the TT-FokI genotype (median: 12.3 ng/mL) had reduced 25(OH)D levels compared to CC/CT carriers (median: 20.8 ng/mL; p = 0.034). These findings suggest that the FokI VDR polymorphism may serve as a potential genetic modulator of cerebrovascular complications in individuals with SCA.

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.