Importance:Pediatric Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder, and early identification of poor responders is critical to improving survival. However, no convenient clinical tools exist to predict individual prognosis using dynamic biomarkers during early treatment. Objective:To investigate the predictive value of early dynamic changes in plasma biomarkers and to develop a prognostic model for children with EBV-HLH. Methods:This retrospective study enrolled 60 newly diagnosed pediatric EBV-HLH patients. We analyzed the longitudinal changes in plasma EBV-DNA (pEBV-DNA), ferritin, and cytokine levels during the etoposide-based induction first-line therapy. Independent prognostic factors were identified using Cox multivariate regression and LASSO, followed by the construction of a prognostic nomogram. Model performance was evaluated through area under the curve (AUC), decision curve analysis, and internal cross-validation. Results:Multivariate analysis identified positive pEBV-DNA at week 2 (w2) and low decreases in ferritin (ΔFerritin.w2) and interferon (IFN)-γ (ΔIFN-γ.w2) as independent predictors of adverse outcomes. A nomogram integrating these three variables demonstrated a superior AUC of 0.834 (vs. 0.677 for pEBV-DNA.w2 alone, P = 0.003). The model successfully stratified patients into low- and high-risk groups with significantly different 3-year event-free survival (84.8% vs. 33.3%, P < 0.001). Interpretation:The proposed model, based on dynamic plasma biomarkers, provides a promising tool for the early risk stratification of pediatric EBV-HLH. Composed of pEBV-DNA, ΔFerritin, and ΔIFN-γ at w2, this nomogram can effectively identify patients at high risk of first-line treatment failure. Given the exploratory nature of this study, these findings require further validation in larger, independent cohorts.

BACKGROUND:Standardized salvage treatments for refractory/relapse Langerhans cell histiocytosis (LCH) remain to be established. Trametinib (TRA) has shown marked efficacy in LCH, but cohort studies regarding efficacy and safety of TRA monotherapy in refractory/relapse LCH were scarce. METHODS/RESULTS:We retrospectively analyzed 22 patients with refractory/relapse LCH treated with TRA monotherapy. Patients were treated for a median of 21.4 months (3.0-51.6 months). Nineteen (86.4%) of 22 of patients remained progression-free during TRA treatment. Sixteen patients stopped TRA (not due to progression or toxicity), of which 10 remained progression free, with median follow-up time of 28.7 months (1.5-44.6 months) after TRA withdrawal, and 6 patients experienced relapse, with median time to relapse from post-TRA withdrawal of 3.7 months (2.7-16.5 months). Two patients continued on TRA at last follow-up and one switched to chemotherapy due to toxicity. Three-year event-free survival was 50.7% (95% CI: 27.7-69.8), with a median follow-up time of 36.4 months (3.0-67.6 months). From TRA initiation to 12 months of treatment, cell-free BRAF/MAP2K1 mutation status in blood presented as negative to negative or positive to negative was correlated with superior event-free survival rate (EFS) rate. Toxicity was tolerable, and adverse events were predominantly skin rash (77.3%), paronychia (22.7%), and diarrhea (13.6%). CONCLUSION:Overall, TRA was effective and safe in the treatment of patients with refractory/relapse LCH, offering a convenient therapeutic alternative.

BACKGROUND:Langerhans cell histiocytosis (LCH) is a rare inflammatory neoplasm most commonly involving bone. However, data on single-system, single-site LCH (SS-s-LCH), particularly with unifocal bone disease, remain limited. Management strategies for unifocal osseous LCH vary globally, and the safety of a watchful-waiting approach is not well-defined. This study aimed to evaluate whether patients with osseous SS-s-LCH can be managed with observation alone without compromising long-term outcomes. METHODS:In this retrospective, multicenter study, we enrolled children with biopsy-proven osseous SS-s-LCH from 7 centers in the Chinese Children's Histiocytosis Group, excluding those with central nervous system (CNS)-risk bone lesions. The primary endpoint was 3-year event-free survival (EFS). Events were defined as disease progression or relapse. RESULTS:The cohort included 134 patients with a median follow-up of 36.0 months. Involved sites were cranial bones (n = 37), vertebrae (n = 33), and other bones (n = 64). At final follow-up, 16 patients experienced an event, yielding a 3-year EFS of 88.1% (95% CI: 81.5%-92.5%). Events included new lesions (n = 14) and primary lesion expansion (n = 2), with 93.8% (15/16) occurring within the first 12 months after diagnosis. EFS did not differ significantly by involved site or mutation status. However, patients staged by PET-CT at diagnosis had a significantly higher 3-year EFS (97.6%) than those staged by conventional imaging (83.7%) (P < .05). Long-term quality of life was satisfactory in all assessed patients. CONCLUSIONS:Watchful waiting is a safe and effective management strategy for children with unifocal osseous SS-s-LCH. Initial staging with PET-CT may be associated with superior EFS, highlighting its potential value in refining risk assessment.

BackgroundPulmonary thromboembolism is rare in children, but can be life-threatening. Timely diagnosis and treatment of pulmonary thromboembolism are crucial for reducing mortality associated with pulmonary thromboembolism in children. While guidelines for pulmonary thromboembolism in adults are available, guidelines for standardized diagnosis and management of pulmonary thromboembolism in children are not. This expert consensus aims to provide recommendations for the management of pulmonary thromboembolism in children based on the current best available evidence.Data sourcesFollowing the World Health Organization Handbook for Guideline Development, the expert panel consisted of 30 members from different clinical areas. The panel identified clinical questions through systematic reviews and expert discussions, systematically reviewed evidence on pulmonary thromboembolism in children, and evaluated the quality of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Using the GRADE Evidence to Decision Framework, the panel made recommendations, considering the effects of interventions, resource use, values and preferences, equity, acceptability, and feasibility.ResultsThe epidemiology, classification, and pathophysiology characteristics are summarized. The expert panel developed 33 recommendations addressing 20 questions related to diagnosis steps, treatment approaches such as anticoagulant therapy, thrombolysis therapy, catheter-based interventional therapy, surgical embolectomy, multidisciplinary team, and treatment of patients with comorbidities, prognosis, education, as well as follow-up. Among these, 18 are weak recommendations based on very low quality evidence, and 15 are good practice statements.ConclusionsThe expert panel provided recommendations for pulmonary thromboembolism in children based on available evidence, which was generally low in quality and volume. The panel urges further research on early identification and diagnosis strategies, preventive and therapeutic regimens, and long-term management for pulmonary thromboembolism.

Langerhans cell histiocytosis (LCH) is an inflammatory and neoplastic disorder. The levels of metabolites in the plasma of children with LCH have not been studied and may be related to disease progression. We committed to find novel pre-diagnostic metabolites in the plasma of LCH children with posterior pituitary involvement (PI). Non-targeted metabolomics sequencing was used to detect specific and pre-diagnostic metabolites in the plasma of children with LCH. Plasma samples from 56 children with LCH and 27 healthy volunteers were enrolled. Plasma samples of children with LCH were divided into three groups: children have no PI or central nervous system-risk (CNS-risk) bone lesions (NPC group), children with CNS-risk bone lesions but without PI (CNS-risk group), and children with PI (PI group). The N-acetylneuraminic acid, lipoamide, L-Glutathione oxidized and indole-3-propionic acids were potential pre-diagnostic metabolites for LCH children with PI in comparison with the healthy volunteers. Metabolites in the plasma of LCH children with PI enriched specific signaling pathways including arachidonic acid metabolism, ferroptosis, etc. Through targeted metabolomics sequencing, we verified that specific metabolites were existed in the stratified involvements of patients with LCH, such as N-acetylneuraminic acid and Vitamin A, which may be related with alteration of blood-brain barrier permeability and LCH disease progression. Through the joint multi-omics analyses, we discovered that the peripheral dendritic cells may have ferroptosis phenomena, which was regulated by osteopontin secreted in the plasma of patients with LCH. Analyses and identification the differential metabolites in the plasma of children with LCH may significantly improve the early diagnosis and stratified treatment of children with pituitary invovlement.

Primary immune thrombocytopenia (ITP) is the most common acquired bleeding disorder in children, and management is challenging when first-line therapy fails. Hetrombopag is an oral thrombopoietin receptor agonist (TPO-RA). This phase 3 randomized, double-blind, placebo-controlled trial evaluated its efficacy and safety in children and adolescents with ITP who had an inadequate response or relapse after prior treatment. Children and adolescents aged 6–17 years were randomized 2:1 to receive once-daily hetrombopag (initial dose 2.5 mg) or placebo for 12 weeks, followed by a 12-week open-label hetrombopag extension. The primary endpoint was the proportion of patients with a platelet count ≥50 × 10⁹/L at Week 10. The key secondary endpoint was the proportion of patients with a sustained platelet response, defined as a platelet count ≥50 × 10⁹/L maintained for ≥6 weeks without rescue therapy between Weeks 5 and 12. Eighty-eight patients were randomized (hetrombopag, n=57; placebo, n=31). At Week 10, 61.4

Background:Velaglucerase alfa is approved in China for treating type 1 Gaucher disease (GD1), but data on its use in Chinese pediatric and adult patients are limited. This study evaluated the safety, efficacy, and pharmacokinetics of velaglucerase alfa in Chinese patients with GD1. Methods:This was a phase IIIb, multicenter, open-label, single-arm, 53-week study (NCT05529992). Patients received intravenous velaglucerase alfa (60 U/kg) every 2 weeks. The primary endpoint was the incidence of serious treatment-emergent adverse events (TEAEs). Secondary endpoints evaluated safety (incidence of TEAEs), efficacy (changes in hemoglobin concentrations, platelet counts, liver and spleen volumes [as percent of body weight, % BW]), and quality of life (QoL). Results:Twenty patients were enrolled (treatment-naïve, n = 16; previously treated, n = 4). Four patients experienced 4 serious TEAEs requiring hospitalization; none were treatment-related. Overall, 19 of 20 patients experienced 104 TEAEs, of which 9 were treatment-related (8.7%; all mild). No TEAEs or deaths led to discontinuation of treatment. Mean (SD) improvements in hemoglobin concentrations (baseline, 10.5 g/dL [2.2]; change, +2.3 g/dL [1.3]; +25.5%), platelet counts (baseline, 59.9 × 109/L [23.4]; change, +42.1 × 109/L [27.7]; +82.3%), normalized spleen (baseline, 5.2% BW [2.6]; change, -3.1% BW [1.6]; -58.4%), and liver volume (baseline, 4.6% BW [1.3]; change, -1.1% BW [0.9]; -21.5%) were observed through Week 53. Nineteen of 20 (95.0%) patients reported improved QoL. Conclusions:Velaglucerase alfa was well-tolerated in Chinese patients with GD1, with no new safety signals, and resulted in improved hemoglobin and platelet levels, as well as liver and spleen volumes.

Immune thrombocytopenia (ITP) is an autoimmune disorder, characterized by immune-mediated platelet destruction and decreased platelet production. To investigate metabolic alterations associated with paediatric ITP and disease chronicity, we performed untargeted plasma metabolomics analysis in 60 newly diagnosed ITP (nITP) patients, 39 chronic ITP (cITP) patients and 39 healthy controls (HC) from Beijing Children's Hospital between October 2020 and August 2024. A total of 30 differential metabolites were identified between ITP patients and HC, with altered tryptophan metabolism among the most significantly enriched metabolic pathways. Random forest analysis achieved an accuracy of 83.9% and a precision of 95.1%. Glycocholic acid demonstrated strong discriminatory performance, with an area under the receiver operating characteristic curve of 0.882 (95% confidence interval: 0.814-0.950). In addition, phosphatidylcholine-related metabolites and sphingolipid-related metabolites were associated with metabolic alterations observed between nITP and cITP. Overall, paediatric ITP was associated with distinct plasma metabolic alterations, particularly involving tryptophan metabolism, bile acid metabolism and lipid metabolism. These findings provide additional insights into metabolic alterations associated with paediatric ITP and disease chronicity.

Background: A portion of children with Langerhans cell histiocytosis (LCH) exhibit recurrent or persistent disease-related fever at their first visit. We aimed to clarify the clinical characteristics, laboratory indicators, prognostic differences, and optimal regimens for these children with fever. Methods: A cross-sectional design (single-center, retrospective, and observational) was adopted for this study. A total of 448 pediatric patients diagnosed with LCH in our hospital from January 2016 to December 2019 were retrospectively enrolled and divided into two groups: children with fever (n=52) and children without fever (n=396). The clinical characteristics, laboratory indicators, and outcomes of regimens for these children were analyzed with SPSS 16.0 software. Results: Children with initial fever had distinct clinical characteristics and laboratory indicators, including an age younger than two years, risk-organ involvement, accompanying hemophagocytic syndrome, and higher levels of cell-free DNA BRAF(V600E) mutation, among others. Patients in the fever group also had a significantly lower treatment efficacy from first-line treatment and a lower 3-year progression-free survival (PFS) rate (approximately 5.22% and 64.23%, respectively; P<0.001). Multivariate Cox regression analysis indicated that fever, risk-organ involvement, skin involvement, ferritin level, and dynamic erythrocyte sedimentation rate were independently prognostic factors for outcomes of first-line treatment. However, the 3-year PFS rates did not differ significantly between patients with fever and without fever after the administration of second-line or target regimens. Conclusions: Among pediatric patients with LCH, those with initial fever exhibit more severe clinical symptoms and worse prognoses after first-line chemotherapy. Alternative strategies may mitigate fever-associated risk, and this possibility should be confirmed through prospective research.

OBJECT:Goal of this study was to investigate distribution of 3 aberrant immunophenotypes of T cells in childhood Hemophagocytic lymphohistiocytosis (HLH), and to find their relations with treatment responses and long-time outcomes. METHODS:Aberrant T cell immunophenotypes presented by patients with HLH at diagnosis during Jan 2018 to Oct 2021 were collected. Distributions of these immunophenotypes among different HLH groups and their relations with first-line therapy responses or lone-time outcomes of patients were studied. RESULTS:T cell populations with aberrant immunophenotypes were found in 40 patients out of 189 (21.2%). Aberrant immunophenotypic patterns were divided into 3 categories: CD38 + HLA-DR + (N=11, 27.5%), clonal expression of TCRVb (N=17, 42.5%), or down regulation of surface CD5 (N=28, 70.0%). Statistical results showed that T cells from patients with EBV-HLH were prone to present 1 or more of these 3 aberrant immunophenotypes ( P <0.001), and that most cases (4/6) with CD4 + T cells with aberrant immunophenotypes were in CAEBV-HLH group. Although plasma levels of IFN-γ were higher in patients with these immunophenotypes ( P =0.01), no significant relation was found between these aberrant T cell immunophenotypes and treatment response or long-time outcome. Besides, no hematologic malignancies developed in patients with aberrant T cell immunophenotypes throughout follow up. CONCLUSION:Patients with HLH frequently show aberrant immunophenotypes of T cells. In most cases, this immunophenotypic patterns have connection to severity, but not outcome of the disease.

Abstract While ETV6 :: RUNX1 -positive acute lymphoblastic leukemia (ALL) is generally associated with favorable outcomes, a subset of patients experience relapse despite receiving standard therapy, underscoring the need for early biomarkers to identify high-risk subgroups. In this retrospective study of 345 consecutive pediatric patients with ETV6 :: RUNX1 -positive ALL treated in accordance with the protocol of the Chinese Children’s Leukemia Group (CCLG-ALL 2008), CD33 expression (CD33 + ) on leukemic blasts was detected in 55.9% of patients and was significantly associated with minimal residual disease (MRD) positivity on day 15 (D15-MRD-positive) (65.2% vs. 42.0%, P < 0.001). Multivariate analysis revealed CD33 + status as an independent risk factor for D15-MRD positivity (odds ratio (OR) = 2.66, 95% confidence interval (CI) 1.66–4.26). Among CD33 + patients, those who were D15-MRD-positive had significantly inferior 5-year and 10-year event-free survival (EFS) relative to those who were D15-MRD-negative (5-year EFS: 91.9% ± 2.4% vs. 100%, P = 0.027; 10-year EFS: 89.2% ± 3.0% vs. 100%, P = 0.014). This prognostic association was not observed in CD33-negative patients. In conclusion, the combination of CD33 + and D15-MRD-positivity may identify a distinct high-risk subgroup within ETV6 :: RUNX1 -positive ALL. Early intervention, potentially including CD33-directed therapy, may represent a promising strategy to improve outcomes in this subgroup, although further validation is warranted.

Abstract Background To evaluate targeted therapy for Langerhans cell histiocytosis (LCH) with maxillofacial manifestations, we conducted a retrospective study of 20 children admitted from January 2016 to June 2021. Methods The maxillofacial LCH exhibited diverse clinical features and laboratory indices. Seventeen patients were refractory to standard treatments, and three patients directly underwent targeted therapy. Sixteen patients with BRAF V600E mutation were treated with dabrafenib, and four patients with MAP2K1 mutation were treated with trametinib. Results The cohort included nine males and eleven females, with a median 0.92 years at diagnosis and 1.70 years at initiation of targeted therapy. Three patients had single-system LCH and 17 patients had multi-system LCH. Lesions affected the mandibular bone in 17 patients, the temporal bone in 12 patients, and the maxilla in 10 patients. Ki-67 expression before targeted therapy correlates with maxillary involvement (coefficient 0.61; P < 0.05). The cfBRAF V600E level after first month of targeted therapy was significantly lower than before targeted therapy (P < 0.001). After a median 18 months of targeted therapy and 22 months of follow-up, 17 patients achieved complete remission, and 3 patients achieved partial remission. The objective response rate was 65%, and the disease control rate was 100%. Five patients experienced progression or reactivation, and ten patients had skin rashes. Conclusion Overall, targeted therapy demonstrated good efficacy with mild tolerable adverse events.

ObjectiveTumor-associated macrophages (TAMs) constitute a significant proportion of the immune cell population within brain tumors. The polarization of macrophages exerts an important influence on the tumor microenvironment (TME). Nevertheless, the specific role of TAMs in sonic hedgehog (SHH) medulloblastoma remains unclear. To investigate the polarization characteristics and effects of TAMs in SHH medulloblastoma, we evaluated the infiltration of M1 and M2 macrophages in SHH medulloblastoma tissues and analyzed the correlation between TAMs recruitment and the clinical outcome of SHH medulloblastoma patients.MethodsWe enrolled a total of 42 patients diagnosed with SHH medulloblastoma. Using multiple immunofluorescence staining on paraffin-embedded sections, we detected the activated phenotype (M1/M2) by monoclonal antibodies for CD68, HLA-DR and CD163. Subsequently, we analyzed the correlation between TAMs and clinical characteristics as well as prognostic factors.ResultsThe median age of 42 patients (31 boys, 11 girls) was 5.3 years (range: 0.8-15.1 years). All patients had confirmed pathological types, including 4 cases of classic medulloblastoma (CMB), 33 cases of desmoplastic/nodular medulloblastoma (DNMB), 3 cases of medulloblastoma with extensive nodularity (MBEN), and 2 cases of large-cell/anaplastic medulloblastoma (LCA). Thirteen cases presented with metastasis at diagnosis, while twenty-nine cases were without metastasis. Four cases had high-risk genetic abnormalities. Different proportions of macrophages were found in the collected medulloblastoma tissues, and large amounts of CD68+HLA-DR+CD163+ cells were found. The study revealed that Mtotal (total macrophages) and Mmix (CD68+HLA-DR+CD163+ cells) were significantly higher in group of patients <5 years old (P < 0.05), and Mtotal in non-metastatic group were significantly higher than that in metastatic group (P = 0.043). M2 macrophages in CMB group were significantly higher than that in DNMB/MBEN group (P = 0.036), M1 macrophages were significantly higher in children without high-risk genetic abnormalities (P = 0.007). Five-year PFS was significantly poorer in patients ≥5 years old and metastatic group (P < 0.05). High Mtotal group had a better 5-year PFS (P = 0.000), whereas high M2 group had both better 5-year PFS and OS (P = 0.001, P = 0.001). Multivariate analysis showed that Mtotal and M2 macrophages were independent prognostic factors for 5-year PFS, and M2 macrophages were an independent prognostic factor for 5-year OS.ConclusionThe increase in total macrophages and M2 macrophages predicts a better outcome of SHH medulloblastoma. TAMs especially M2 macrophages might be a therapeutic target for SHH medulloblastoma.

Isolated central nervous system (CNS) involvement due to posttransplantation proliferative disorder (PTLD) is even rarer, with only a few cases reported in the literature. CNS involvement in patients with mature B-cell non-Hodgkin's (NHL) and PTLD confers a significantly worse prognosis as compared to patients without CNS lymphoma disease. Treatment of CNS lymphoma (CNSL) is challenging due to resistance to conventional cytotoxic and intrathecal chemotherapy. Here, we report the successful use of intrathecal rituximab in two pediatric cases of CD20 + isolated CNSL that had failed to respond to standard chemotherapy, intravenous rituximab and Epstein-Barr virus (EBV)-specific cellular therapy. However, after repeated intrathecal administration of rituximab, both patients’ clinical symptoms were alleviated, which has created opportunities for further treatments. We emphasise that intrathecal rituximab may be a safe and promising strategy for the treatment of pediatric patients with CD20 + isolated CNSL. The literature on this topic was also reviewed.

BACKGROUND:Pediatric patients with autoimmune lymphoproliferative immunodeficiencies (ALPIDs) who exhibit autoimmune cytopenias are frequently diagnosed with immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), or Evans syndrome (ES). These conditions generally necessitate long-term immunosuppressive therapy using medications that are often ineffective and highly toxic before the diagnosis of ALPIDs. A less harmful treatment strategy is needed. METHODS:In this study, we described 23 pediatric patients whose initial symptom was autoimmune cytopenias and who were treated with sirolimus as monotherapy (1.5-4 years) upon being diagnosed with ALPIDs. RESULTS:Children with ALPIDs achieved a sustainable response in immune-related cytopenias and lymphoproliferation manifestations within 3 months of sirolimus monotherapy. The complete response (CR) rate for cytopenias was higher compared to lymphoproliferative manifestations. Thrombocytopenia achieved CR more quickly than anemia and neutropenia. Following sirolimus treatment, there was an increase in the proportion of CD4+CD25+Foxp3+ Tregs and serum TGF-β, while a significant reduction in the DNT ratio was observed. CONCLUSION:Sirolimus resulted in CR and long-lasting responses in most pediatric ALPIDs patients, suggesting it could be considered as a first line for patients requiring prolonged therapy. The increase in Tregs and decrease in DNT after sirolimus treatment may provide insights into the underlying mechanisms of sirolimus in ALPIDs.

Background Minimal residual disease (MRD) level after induction therapy is a key independent prognostic factor in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), with lower MRD burden strongly associated with superior event-free and overall survival. Blinatumomab, a bispecific CD19/CD3 T-cell engager, has demonstrated potent MRD clearance and clinical benefit when integrated into frontline regimens. We hypothesized that administering blinatumomab after a reduced-intensity induction chemotherapy—replacing components of conventional induction—could enhance MRD eradication while reducing cumulative chemotherapy exposure in children with intermediate- or high-risk BCP-ALL. Methods Between April 2024 and May 2025, we conducted a multicenter, single-arm, prospective trial (ChiCTR2400083570) under the Chinese Children's Leukemia Group (CCLG), enrolling patients with newly diagnosed BCP-ALL. Eligibility criteria included: (1) intermediate-risk (MR) with MRD ≥1% by multiparametric flow cytometry (MFC) at day 15; or (2) high-risk (HR) per the Chinese Children's Leukemia Group 2018-ALL (CCLG-2018-ALL) criteria at day 15. All patients received a reduced-intensity induction chemotherapy: daunorubicin (2 doses), vincristine (2 doses), pegaspargase (1 dose), and prednisone about 2 weeks. This was followed by continuous intravenous blinatumomab (15 μg/m²/day) for 2 weeks in MR patients (replacing the subsequent 2-week phase of induction) or 4 weeks in HR patients (replacing the subsequent 2-week phase and the first course of early consolidation [CAML1]). Subsequent chemotherapy resumed 2 weeks after blinatumomab completion. The primary endpoint was MRD negativity at the end of induction in MR patients or at the end of consolidation in HR patients. MRD was assessed centrally using MFC (sensitivity 1×10⁻⁴) and next-generation sequencing (NGS) of immunoglobulin genes (sensitivity 1×10⁻⁶). Results A total of 202 patients were enrolled (median age: 5.8 years; range: 1.1–15.7; 51.5% female); 100 MR and 102 HR. Baseline genetic alterations included ETV6::RUNX1 (13.4%), KMT2A rearrangements (5.9%), and BCR::ABL1 fusion (6.9%). Mean MFC MRD at day 15 was 12.3% (range: 0–80.5%). Complete remission rate was 99.0% (200/202). MRD negativity was achieved in 95.0% (192/202) by MFC and 70.0% (112/160) by NGS at end of induction. In the MR group, MRD negativity rates were 97.0% (MFC, 97/100) and 73.1% (NGS, 57/78). In the HR group, MRD negativity was 93.1% (MFC, 95/102) and 67.1% (NGS, 55/82) at end of induction, improving to 95.1% (MFC, 97/102) and 81.7% (NGS, 67/82) at the end of consolidation. Among 76 HR patients with serial monitoring, MFC MRD negativity increased from 76.3% (58/76) at week 2 to 93.4% (71/76) at week 4 of blinatumomab. Grade ≥3 non-hematologic toxicities included infection (20.8%), sepsis (6.9%), hepatotoxicity (7.9%), cytokine release syndrome (CRS, 4.5%), pancreatitis (2.0%), hypofibrinogenemia (2.0%), and ICANS (0.5%). Treatment interruption occurred in 10 patients (5.0%), primarily due to CRS (n=4) or hepatotoxicity (n=2). With a median follow-up of 8.4 months, 10 patients (5.0%) proceeded to allogeneic hematopoietic stem cell transplantation (allo-HSCT): 2 from the MR group (due to rising MRD, including 1 with BCR::ABL1 fusion and 1 with ETV6:: RUNX1 fusion) and 8 from the HR group (due to MRD persistence, including 3 with KMT2A rearrangement, 1 with MEF2D rearrangement, 1 with DUX4 rearrangement, and 3 with no detectable fusion gene). Among the remaining 192 patients, 100% were MFC MRD-negative and 99.0% NGS MRD-negative at last assessment. Conclusion In Chinese children with intermediate- or high-risk BCP-ALL, integrating blinatumomab after a reduced-intensity induction chemotherapy achieves high rates of deep molecular remission with a favorable safety profile. These findings support the potential of immunotherapy-driven frontline strategies to improve early outcomes and reduce long-term toxicity in pediatric BCP-ALL.

Ruxolitinib (RUX) has demonstrated efficacy in haemophagocytic lymphohistiocytosis (HLH) patients, but large cohort studies regarding its clinical application in children with Epstein-Barr virus-associated HLH (EBV-HLH) remain scarce. This retrospective study analysed the efficacy and safety of RUX-based regimen (n = 53) and compared it with adjusted HLH-94 chemotherapy (n = 42) in the treatment of paediatric EBV-HLH. The patients treated with the RUX-based regimen received RUX monotherapy as front-line therapy. Additional methylprednisolone and etoposide would be added in sequence if the response was unsatisfactory. At 8 weeks of therapy, the overall response rate of the RUX group was comparable to that of the traditional chemotherapy group (84.9% vs. 76.2%, p = 0.282), with a 12-month survival rate of 92.2% (95% CI: 80.6-97.0) and 87.6% (95% CI: 72.1-94.5) (p = 0.595). In the RUX group, 56.6% of patients achieved sustained remission without requiring etoposide during a median follow-up of 17.2 months. Among these patients, 93.3% had primary EBV infection. The RUX-based regimen was well-tolerated, exhibiting significantly lower incidence of myelosuppression and secondary infection than adjusted HLH-94 chemotherapy (35.8% vs. 95.2%, p < 0.001; 28.3% vs. 59.5%, p = 0.002). Overall, our preliminary results indicated that EBV-HLH children treated with the RUX-based regimen demonstrated favourable efficacy while significantly reducing treatment-related adverse events.