Systemic Epstein-Barr virus-positive (EBV-positive) T/NK cell lymphoproliferative diseases of childhood (sEBV+T/NK-LPD) are a spectrum of rare diseases that have highly variable biological behavior, from indolent conditions to highly aggressive malignancies. Clinicians currently face substantial challenges in promptly assessing disease severity and predicting patient outcomes, leading to limitations in treatment planning. To address this challenge, we constructed a comprehensive triage system to aid in rapid clinical interventions. The study included 156 patients with newly diagnosed sEBV+T/NK-LPD from 42 institutions. An independent prospective cohort of 35 newly enrolled patients was further included to evaluate the model's performance. An additional 45 patients from the literature and 18 patients who underwent hematopoietic stem cell transplantation were included to test the score's generalizability. An integrative machine learning strategy was applied to identify robust and optimal factors and to integrate multiple algorithms to enhance the system's performance and stability. This system, termed COLLAPSED, identifies critical factors and provides a stable, high-performing ensemble. This model was validated externally and simplified into a risk score to improve interpretability and accessibility. The COLLAPSED system substantially enhances clinicians' ability to rapidly and precisely identify high-risk patients, thus enabling timely clinical decision-making and expedited initiation of potentially lifesaving treatments.

PURPOSE:Molecular profiles of sarcomas in Chinese children remain unknown. The Chinese Pediatric Precision Oncology Group (CPPOG) is a prospective precision medicine program aimed at defining tumor molecular profiles in pediatric oncology patients across China, which aids diagnosis and treatment decisions. Herein, we report, to our knowledge, the first data from the CPPOG trial. METHODS:Panel sequencing (830-gene DNA panel and 395-gene RNA panel) was performed on 214 tumors from 210 patients with sarcoma from 11 centers, between April 2021 and January 2022 in China. This study was prospectively analyzed to characterize subtype-specific somatic alterations and pathways. Molecular features among subgroups concerning response to treatment and pathologic characteristics were also identified. RESULTS:Genomic profiling revealed molecular aberrations in the patients: 88.3% harbored at least one somatic or germline alteration; 51.4% carried gene fusions (including 37 novel fusion variants); 46.3% possessed actionable therapeutic targets; 9.5% exhibited germline variants; and 14.3% had modified diagnoses based on molecular findings. In this study, the most common genetic alterations were TP53 mutation and EWSR1-FLI1 fusion. The most common activated pathways were TP53, PI3K, and RTK-RAS in pediatric sarcomas. Anaplastic embryonal rhabdomyosarcomas had special molecular characteristics, with high TP53, MYCN, and MYCL gene alteration frequencies. The mutation frequencies of TP53 and NRAS were notably higher in patients who had undergone disease progression, relapse, or metastasis. Moreover, MYC, MYCN, and MDM2 alterations were more frequent in tumors with mitotic figures >50/3 mm2. CONCLUSION:Our study reveals the preliminary molecular landscape of Chinese pediatric sarcomas, indicating that molecular changes may represent different therapeutic responses and pathologic characteristics may correlate with molecular characteristics, suggesting the need for panel sequencing for pediatric sarcoma.

BACKGROUND:Neuroblastoma is the most common extracranial solid tumor in children and exhibits substantial clinical heterogeneity. Although key genetic alterations such as N-Myc proto-oncogene protein amplification and anaplastic lymphoma kinase mutations are known drivers of neuroblastoma, their clinical utility is limited by population-specific genetic diversity. To address this, we propose a "function-over-gene" strategy by evaluating extracellular matrix (ECM)-related gene sets as molecular biomarkers, aiming to overcome the limitations posed by genetic heterogeneity and provide novel prognostic insights. METHODS:We integrated data from a single-center cohort and the TARGET database. Cox regression models were used to assess the prognostic value of ECM gene alterations and their association with clinical outcomes. Gene set enrichment analysis (GSEA) was employed to identify ECM-related gene sets, followed by transcriptomic analysis to explore downstream regulatory pathways. RESULTS:In the single-center cohort, ECM gene mutations were potentially associated with bone and lymph node metastases and emerged as an independent predictor of poor prognosis (HR=2.7, P =0.02) in multivariate analysis. Validation using the TARGET cohort confirmed the prognostic relevance of the ECM gene set (HR=1.55, P =0.0083) and revealed its involvement in modulating the tumor microenvironment via immune and complement pathways. CONCLUSION:ECM gene signatures serve as robust prognostic markers across populations. This function-based approach offers a novel perspective to address genetic heterogeneity and provides a theoretical foundation for ECM-targeted combination therapies.

Managing persistent soft tissue residual disease in high-risk neuroblastoma (HR-NB) remains a clinical challenge, particularly when conventional response assessments suggest remission but residual lesions persist. Determining whether such lesions represent inactive treatment-related changes or viable tumor has important implications for subsequent management. We report a 4-year-and-11-month-old girl with HR-NB who received multimodal therapy, including induction chemotherapy, surgery, radiotherapy, autologous stem cell transplantation, and seven cycles of dinutuximab beta-based immunotherapy. Following treatment, standard evaluations demonstrated complete bone marrow clearance and a ^123I-MIBG Curie score of 0, suggesting an excellent systemic response. However, a persistent paravertebral residual lesion remained detectable on imaging. Notably, ^68Ga-DOTA-NOC PET/CT demonstrated persistent tracer uptake despite negative ^123I-MIBG findings, creating an imaging discordance that raised concern for residual viable disease. Subsequent “third-look” surgical resection confirmed viable neuroblastoma within the lesion. Pathological examination revealed a markedly increased Ki-67 labeling index compared with the post-induction specimen (50% versus 8%), indicating persistent proliferative activity and suggesting biological heterogeneity within the residual lesion. This case highlights the diagnostic and therapeutic challenges posed by persistent soft tissue residual lesions after immunotherapy. The discordance between ^123I-MIBG and ^68Ga-DOTA-NOC imaging suggests that conventional imaging alone may not fully characterize selected residual lesions. In patients with persistent masses and discordant imaging findings, multimodal functional imaging may provide complementary information to guide clinical decision-making. The favorable outcome observed in this patient, who remains in sustained remission following surgical resection without additional antitumor therapy, supports consideration of an integrated management strategy combining multimodal imaging assessment and appropriately timed surgical intervention for selected cases of persistent residual disease.

Background:Magnetic resonance imaging (MRI) is an ideal method for the detection of osteonecrosis in children with acute lymphoblastic leukemia (ALL), but some children struggle to adhere to the procedure due to its lengthy examination time. This study evaluated the feasibility of synthetic MRI for knee examinations in children with ALL. Methods:This prospective study included 33 children with ALL who underwent conventional and synthetic MRI. Participants were categorized into Group A (>8 years, n=23) and Group B (≤8 years, n=10). Scan time, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), motion artifacts, image quality score, lesion detection, and T2 values were compared using paired t-tests, Wilcoxon signed-rank tests, Cohen's kappa, and Bland-Altman analysis, with Bonferroni correction (α=0.003). Results:Synthetic MRI significantly reduced scan time (Group A: 286±74 vs. 504±64 s, P<0.001; Group B: 254±8 vs. 461±17 s, P=0.002). No significant SNR or CNR differences were found between synthetic and conventional T1-weighted imaging (T1WI) (P>0.003). Synthetic proton density-weighted imaging (PDWI) showed lower SNR (P<0.003) but similar CNR (P>0.003). In T1WI, motion artifacts were comparable between synthetic and conventional MRI in Group A (P=0.166) but were more pronounced with synthetic MRI in Group B (P=0.038). In PDWI, synthetic images exhibited significantly greater motion artifacts in both Group A and Group B (P=0.011 and P=0.023, respectively). Image noise was higher in synthetic T1WI and PDWI (P<0.050). Lesion detection showed excellent agreement (κ=0.86-0.96), though two Group B cases were nondiagnostic. T2 values showed no significant inter-method differences in either group (P>0.003). Conclusions:For pediatric leukemia patients capable of maintaining stillness, synthetic MRI shortens acquisition time while preserving diagnostic accuracy and quantitative precision. However, due to motion susceptibility, its clinical use should be limited to cooperative children.

Poor early treatment response in T-cell lymphoblastic lymphoma (T-LBL) is associated with an unfavorable prognosis. This multicenter prospective study evaluated the efficacy of the response-adjusted Chinese Children's Cancer Group (CCCG–LBL-2016) protocol for pediatric T-LBL and examined clinical and molecular prognostic factors. Clinical and laboratory data from seven pediatric oncology centers were analyzed. A sub-cohort of 23 patients underwent exploratory integrated genomic analysis, including targeted next-generation sequencing, RNA sequencing, and copy-number array analysis. Survival was evaluated using the Kaplan–Meier method, and prognostic factors were analyzed using multivariable Cox proportional hazards regression. A total of 163 patients (median age: 108 months; 116 males, 47 females) were enrolled, most with advanced disease (stage III: 81.0

mRNA-targeted tumor drugs,featuring various types and distinct antitumor mechanisms of action,have demonstrated significant potential in tumor immunotherapy.Currently,nearly one hundred registered clinical trials initiated by pharmaceutical companies or sponsors are being conducted worldwide,and these trials have shown impressive efficacy.In China,multiple registered clinical trials have been conducted in the past two years,reflecting rapid development.Although mRNA tumor drugs still face certain challenges,the advantages of mRNA technology are clear,promoting the integrated development of immunotherapy,gene therapy,and cell therapy.With ongoing technological innovation and optimization,the demand for"mRNA therapy"for tumor prevention and treatment is expected to be met.This review discusses the distinct mechanisms of action,progress in basic research,clinical advancements,challenges,and future perspectives of both prophylactic and therapeutic mRNA cancer vaccines.It aims to enhance understanding of research progress in mRNA technology for oncological drug applications and to provide insights for future research and product development of mRNA-based interventions in oncology.

Background Neuroblastoma is the most common extracranial solid tumor in childhood. With advances in risk-adapted multimodal therapy, survival outcomes for high-risk neuroblastoma have improved substantially. However, prolonged survival has been accompanied by an increasing incidence of therapy-related second malignant neoplasms, which represent a serious late complication and a growing clinical challenge.Case presentation We report a rare case of an extremely early-onset secondary malignancy in a young child treated for high-risk neuroblastoma. A 3-year-and-4-month-old girl achieved complete remission after intensive multimodal therapy for stage IV high-risk neuroblastoma. Remarkably, only one month after completion of treatment, she developed therapy-related acute myelomonocytic leukemia (AML, FAB M4 subtype). Bone marrow evaluation revealed high-risk molecular features, including a t(9;11)(p21;q23) translocation resulting in a KMT2A-MLLT3 (MLL/AF9) fusion and concomitant EVI1 overexpression.Results The patient was treated with intensive AML-directed chemotherapy followed by allogeneic hematopoietic stem cell transplantation. She achieved complete hematologic and molecular remission, with sustained negativity of minimal residual disease. At the last follow-up in July 2025, she remained in continuous remission for 51 months and had returned to normal school life.Conclusion This case highlights an exceptionally short latency of therapy-related AML as a second malignant neoplasm following modern intensive treatment for high-risk neuroblastoma. It underscores the need for heightened vigilance for secondary malignancies even during the early post-treatment period and emphasizes the importance of long-term surveillance strategies in neuroblastoma survivors. Early recognition and timely allogeneic transplantation may offer curative potential in selected high-risk cases. Despite the overall poor prognosis associated with therapy-related acute myeloid leukemia (t-AML), this patient achieved long-term survival following allogeneic hematopoietic stem cell transplantation, highlighting the potential for successful outcomes even in high-risk cases.

An 11-year-old boy with relapsed, poorly differentiated left adrenal neuroblastoma presented with multiple bone metastases, demonstrated by an 18 F-MFBG PET/CT with a Curie score of 4, despite prior multimodal therapy. He was subsequently enrolled in a phase 1 dose-escalation trial of 211 At-MABG-targeted alpha therapy. Follow-up 18 F-MFBG PET/CT revealed the resolution of most lesions and markedly decreased tracer uptake at the residual site, reducing his posttreatment Curie score to 1. This case highlights the therapeutic potential, safety, and feasibility of repeated, low-dose 211 At-MABG-targeted alpha therapy for pediatric relapsed neuroblastoma.

BACKGROUND:Invasive pulmonary fungal infections (IPFIs) in immunocompromised children carry high morbidity and may interrupt life-saving chemotherapy or haematopoietic stem cell transplantation (HSCT). Evidence on perioperative risk stratification for surgical management is limited. PATIENTS AND METHODS:We conducted a single-center retrospective cohort study of patients < 16 years with proven/probable IPFI who underwent lung resection from 2017 to 2025, with fungal infection confirmed by pathology. Preoperative clinical variables, laboratory tests and CT features were collected. Outcomes included intraoperative blood transfusion, severe postoperative complications, 90-day mortality and time to resumption of chemotherapy/HSCT. An exploratory preoperative weighted risk score was derived and evaluated. RESULTS:Thirty-three patients were included (median age 9 years; 75.8% male). Aspergillus was the most common pathogen (72.7%); 57.6% had centrally located lesions and 12.1% had multilobe involvement. Procedures were mainly lobectomy (66.7%) or wedge resection (30.3%), with VATS in 45.5%. Peripheral lesion location was associated with less intraoperative transfusion, while hemoptysis and central lesion predicted delayed resumption of chemotherapy/HSCT; preoperative platelet count < 100 × 109/L, multilobe involvement and central location were significantly associated with severe complications. Integrating these independent findings, a 0-8 point composite risk score was constructed (optimism-adjusted C-index: 0.948). The model effectively stratified outcomes: severe complications occurred in 0% (low), 26.7% (moderate) and 75% (high) (p = 0.004). Among survivors, median time to resume chemotherapy/HSCT was 18 days (low) versus 35 days (moderate) versus 78 days (high) (p < 0.001). All 90-day deaths occurred in the high-risk group (p < 0.001). CONCLUSIONS:Surgery can support source control and timely oncologic treatment in selected paediatric IPFI. A simple, statistically validated preoperative score may help anticipate surgical risk and recovery time and identify a high-risk subgroup with poor short-term outcomes.

ABSTRACT:Asparaginase-associated pancreatitis (AAP) is a significant complication in pediatric acute lymphoblastic leukemia (ALL) therapy, often leading to treatment delays or discontinuation. This study aimed to identify AAP risk factors, assess outcomes after first and second episodes, and evaluate the impact of asparaginase rechallenge. We retrospectively analyzed 7640 patients (aged 1 month to 18 years) treated under the Chinese Children Cancer Group ALL 2015 protocol. Patients were stratified as low risk (LR), intermediate risk (IR), or high risk (HR) based on clinical features and measurable residual disease (MRD). AAP was categorized as early or late onset depending on treatment phase. Older age and IR/HR status were independent risk factors for AAP. The cumulative AAP incidence was 2.2% in LR and 5.8% in IR/HR groups. Among 298 patients who developed AAP, 92 were rechallenged with asparaginase; second episodes occurred in 20.8% of LR and 33.8% of IR/HR patients, with no increase in severity. Lack of rechallenge and day 46 MRD of ≥0.01% were independently associated with inferior event-free survival (EFS). Among patients with early-onset AAP, those who were rechallenged had superior 5-year EFS than those who were not rechallenged (80.1% vs 60.2%; P = .003). Similarly, among IR/HR group, those who were rechallenged had better 5-year EFS than those who were not rechallenged (82.4% vs 60.6%; P = .004). IR/HR patients with early-onset AAP who were not rechallenged had especially poor outcomes (5-year EFS, 53.3%). These findings support considering asparaginase rechallenge in IR/HR patients with early-onset AAP when alternative therapies are limited. This trial was registered at www.chictr.org.cn as #ChiCTR2000032211.

Retinoblastoma (RB) is the most common primary intraocular malignancy in children and mostly initiates with biallelic inactivation of the RB1 gene. Hereditary retinoblastoma accounts for 40% of all cases, with only 6%-10% of patients having a positive family history. The proband, a Chinese Tibetan boy, was diagnosed with RB for leukocoria. The RB1 gene mutations were screened due to disease recurrence. A novel germline donor splicing site mutation (c.861 + 2T>A) from his father was identified by Sanger sequencing and a novel somatic duplication mutation in exon 2 221-224 (p.W75Cfs*36) by next-generation sequencing (NGS). The proband's younger brother manifested bilateral RB and also carried the same germline mutation. To further explore the possible pathogenicity of the novel germline RB1 mutation (c.861 + 2T>A) in RB development, mutation analysis, bioinformatics analysis, and immunohistochemistry were performed. After RB1 cDNA was amplified, the abnormal script was found to be smaller than the normal script. Compared with normal samples, Sanger sequencing revealed a deletion of 143 bp in the abnormal script. In comparison to healthy individuals, patients exhibited a reduction in the mRNA expression levels of the RB1 gene. The three-dimensional structure predicted by iterative threading assembly refinement (I-TASSER) indicates significant changes in the spatial structure of abnormal proteins after mutation. No expression of RB1 was found in tumor tissue by immunohistochemistry evaluation. Therefore, the novel germline donor splicing site mutation (c.861 + 2T>A) has been confirmed to be a pathological mutation.

Neuroblastoma (NB), the most common extracranial solid tumor in children, is characterized by remarkable cellular heterogeneity and clinical variability ranging from spontaneous regression to aggressive progression and relapse. Despite advances in multimodal therapies, including surgery, chemotherapy, radiotherapy, differentiation therapy, and immunotherapy—treatment resistance remains the principal barrier to improving survival in high-risk patients. Recent single-cell and spatial multi-omics studies have revolutionized our understanding of NB by revealing its developmental origins, lineage hierarchy, and adaptive evolution under therapeutic pressure. These technologies have delineated distinct cellular states along an adrenergic–mesenchymal continuum and uncovered the dynamic interplay between tumor cells and their microenvironment. Genetic instability, epigenetic reprogramming, and metabolic plasticity cooperate with immune and stromal remodeling to drive tumor persistence and relapse. At the molecular level, mechanisms such as MYCN-driven chromatin remodeling, super-enhancer reorganization, bypass signaling activation, quiescent persister programs, immune checkpoint engagement, and metabolic rewiring collectively enable therapeutic escape. Importantly, these processes are reversible, highlighting tumor plasticity as both a hallmark and a potential vulnerability of NB. Integrating single-cell transcriptomics, epigenomics, and spatial profiling provides an unprecedented framework to map resistance evolution, identify lineage-specific vulnerabilities, and guide rational combination strategies. Targeting epigenetic regulators, metabolic checkpoints, and immune suppressive networks in a temporally coordinated manner holds promise for converting NB from an adaptive to a controllable disease.

The Realgar-Indigo Naturalis formula (RIF) is a proprietary Chinese medicine, which is one of the important drugs in the treatment of pediatric acute promyelocytic leukemia (APL). However, the dose of RIF in clinical application is not uniform and the long-term effectiveness and safety of combining RIF with all-trans retinoic acid (ATRA) in a larger population of pediatric APL patients remains undocumented. We conducted a multicenter single-arm clinical trial (ChiCTR-OIC-16010014) in China. Individuals newly diagnosed with APL were treated with CCCG-APL-2017 protocol which is based on RIF and ATRA in consolidation. The event-free survival (EFS) and overall survival (OS) outcomes were evaluated. We recruited 200 patients diagnosed with APL. The six-year OS rate was 100% in the low-risk (LR) group and 97.6% in the high-risk (HR) group. The six-year EFS rate was 98.3% in the LR group and 97.6% in the HR group. Plasma levels of arsenic remained stable after the administration of RIF at a dosage of 60 mg/kg/d for seven days and returned to baseline levels within fourteen days after discontinuation of RIF administration, which is consistent with a concentration of 135 mg/d/kg. Furthermore, controlling white blood cells (WBC) to maintain levels at or below 30 × 109/L during induction therapy can decrease the incidence of induced differentiation syndrome (DS) or alleviate its symptoms. Our study demonstrated that the CCCG-APL-2017 protocol, which combines RIF with ATRA, is both effective and safe in treating children with APL.

Neuroblastoma (NB) is a prevalent extracranial solid tumor in pediatric patients. Of these, the MYCN-amplified type has a poor treatment response and prognosis. To enhance therapeutic efficacy and prognostic outcomes, numerous research teams have undertaken extensive investigations through various pathways and directions. Among these, ferroptosis has recently emerged as a significant area of research focus.Ferroptosis, a type of iron-dependent cell death, is primarily caused by lipid peroxides. This study intends to develop a prognosis model based on MYCN-amplified NB and ferroptosis-related genes (FGs). Data for this study were sourced from the TARGET and FerrDb databases. Lasso regression algorithms and univariate COX analysis were leveraged to determine feature genes; multivariate COX analysis was employed to develop a prediction model and risk scores; and receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were utilized to assess the predictive ability of the model. Furthermore, discrepancies in immune cell infiltration (ICI) between the high-risk (HR) and low-risk (LR) populations were assessed via CIBERSORT analysis. Finally, experiments were conducted on MYCN-amplified and MYCN non-amplified cells so as to validate the differential expression of the gene. A prediction model was constructed and risk scores were calculated based on 4 genes (LIFR, TP53, NRAS, and OSBPL9). The HR group, which was stratified by the median score, had a lower overall survival rate than the LR group.The differences in expression of each gene between MYCN-amplified and MYCN non-amplified cells were further confirmed through cell experiments and qPCR. The prediction model in this study can be employed to forecast the prognosis of MYCN-amplified NB. These genes may represent promising new ferroptosis-related intervention targets (FITs) in treating MYCN-amplified NB, with the potential to improve patient outcomes.

ObjectiveHereditary spherocytosis (HS) is a common red blood cell membrane disease. It is currently clear that mutations in genes such as ANK1, SPTB, SPTA1, SLC4A1, EPB4.2 can cause the loss of their corresponding encoded proteins. However, there is a lack of reports in China on the association analysis between HS genotypes and clinical phenotypes, aiming to reveal whether there are differences in the corresponding clinical phenotypes of the same disease when genotypes are different.Methods35 children with HS who underwent complete whole exome gene sequencing in the Department of Pediatric Hematology at West China Second Hospital of Sichuan University from February 2014 to February 2024. Grouping according to different mutated genes/mutation types, and statistical analysis of blood routine and liver function indicators between different groups; Mann Whitney test analysis was used for inter group data processing, and significant differences were considered when both sides were p < 0.05.ResultsCompared with the SPTB group, the ANK1 group had significantly lower RBC (p = 0.021) and HGB (p < 0.01), but the differences in other indicators were not statistically significant (p > 0.05).ConclusionsAfter excluding potential influencing factors such as splenectomy, the anemia symptoms in ANK1-HS patients were more severe than those in SPTB-HS patients. However, there was no statistically significant difference in indicators between HS patients with different types of gene mutations.

Congenital leukemia is an exceptionally rare malignancy with an incidence below five per million births and poor prognosis, especially in cases with KMT2A rearrangements. Spontaneous remission (SR) is an uncommon phenomenon; since 1996, only five SR cases with KMT2A rearrangements have been reported worldwide. We describe a neonate with congenital AML-M5 carrying a KMT2A-MLLT3 fusion, who achieved SR without chemotherapy but relapsed at 5 months with extensive extramedullary disease. At relapse, we performed the world’s first single-cell transcriptomic sequencing of SR-associated congenital leukemia. Analysis showed no proliferative advantage in leukemic progenitors but marked autophagy upregulation and an incomplete immune evasion phenotype, suggesting transient dormancy and partial susceptibility to cytotoxic T-cell surveillance. The patient subsequently achieved molecular remission with CCLG-AML-2024 chemotherapy and remained disease-free following matched unrelated HSCT at 12 months. This case highlights the fragile balance between leukemic clones and host immunity in early life, suggesting autophagy activation and immune sensitivity as natural restraints on leukemogenesis. It emphasizes that SR represents a temporary pause rather than cure, requiring close molecular monitoring, and provides the first single-cell atlas of SR-type congenital leukemia, offering new directions for immunomodulatory and autophagy-targeted therapies in high-risk KMT2A-rearranged leukemia.