Objective:To assess the safety profile of administering intrathecal (IT) chemotherapy concurrently with blinatumomab in pediatric patients with acute lymphoblastic leukemia (ALL). Methods:This retrospective analysis included 93 pediatric ALL patients treated between February 2021 and May 2025 who received blinatumomab. Results:Of the 93 enrolled patients (median [Q1, Q3] age, 6 [4, 12] years), 42 (45%) were given IT chemotherapy concurrently, while the remaining 51 (55%) served as controls. Neurotoxic events occurred in eight patients (8.8%) overall, with no statistically significant difference between the concurrent IT and control groups (12% vs. 6%, p = 0.461). However, receiving IT chemotherapy on Day 1 of blinatumomab was strongly associated with neurotoxicity (OR = 15.6; 95% CI: 2.96-87.8; p = 0.001). Additional univariate predictors included CD4+ T-cell count (OR = 0.03; 95% CI: 0.00-0.50; p = 0.045), serum albumin (OR = 1.17; 95% CI: 1.02-1.39; p = 0.042), and bone marrow blast percentage (OR = 1.05; 95% CI: 1.01-1.09; p = 0.017). Multivariate analysis identified Day 1 concurrent IT administration as an independent risk factor (OR = 12.5; 95% CI: 1.45-131; p = 0.023). Conclusions:Initiating IT chemotherapy on the same day as blinatumomab infusion significantly increases the risk of neurotoxicity in pediatric ALL patients.

BACKGROUND:B-cell lymphoblastic lymphoma (B-LBL) represents a rare variety of non-Hodgkin lymphoma, with limited research on its biology, progression, and management. METHODS:A retrospective analysis was performed on the clinical characteristics of 256 patients aged ≤18 years who received treatment under the China Net Childhood Lymphoma (CNCL)-NHL-2017-lymphoblastic lymphoma regimen from April 2017 to March 2023. RESULTS:Among the 256 patients, the median age at diagnosis was 5.0 years, with a slight male predominance. Subcutaneous tissues, skin, and osteolytic bone were the most common sites of the disease. More than 90% of patients exhibited disseminated disease (Stage III or IV). Approximately 19.9% of the diagnosed patients exhibited central nervous system involvement. Adverse events were observed in 33 patients (12.9%), with disease progression or relapse occurring in 10.2% of cases, particularly linked to unfavorable outcomes in instances of early relapse or progression. Salvage chemotherapy combined with immunotherapies, followed by bridging hematopoietic stem cell transplantation, significantly improved the prognosis of relapse and disease progression in children. Overall, the follow-up time was 37.6 (Q1-Q3, 28.9-38.0) months, and 3-year event-free survival rate and overall survivals were 86.3% ± 2.5% and 95.2% ± 1.5%, respectively, with a treatment-related mortality of 1.6%. Multivariate analysis showed that poor prednisone response and no complete remission on Day 33 of induction were risk factors for poor prognosis. CONCLUSION:The CNCL-NHL-2017-lymphoblastic lymphoma regimen was effective in children with B-LBL. The response to initial treatment is vital for improving prognosis in patients with B-LBL.

The application of targeted therapy with arsenic and all-trans retinoic acid (ATRA) has significantly improved outcomes in pediatric acute promyelocytic leukemia (APL), but relapse remains a major obstacle to cure. This study aimed to identify risk factors for relapse in pediatric APL and to evaluate the relationship between arsenic concentration and relapse. In this multicenter retrospective study, a total of 566 pediatric patients with newly diagnosed APL treated with the CCLG-APL 2016 or CCLG-APL 2018 protocol were enrolled. The median follow-up was 68.0 months, and 44 patients experienced relapse. The analysis showed complex karyotypes (≥ 3 additional chromosomal abnormalities) (HR = 3.238, 95% CI: 1.134–9.244, P = 0.028) and MCR ≥ 72 days (HR = 1.995, 95% CI: 1.132–3.757, P = 0.024) were independent risk factors for relapse. Logistic regression indicated that arsenic trioxide (ATO) used during induction was associated with a lower relapse risk compared to Realgar-Indigo naturalis formula (RIF) (OR = 0.310, 95% CI: 0.105–0.916, P = 0.034]. In 64 patients with arsenic monitoring, blood arsenic levels on days 7, 14, and 28 were significantly higher in ATO group than the RIF group (all P < 0.01), and were significantly lower in the relapse group compared to the non-relapse group ( P = 0.031, 0.036, 0.034, respectively). ROC analysis identified a blood arsenic cutoff of < 25.6 ng/mL after 7 days of induction as predictive of higher relapse risk. Our study confirmed risk factors for relapse in pediatric APL, and suggested that maintaining a blood arsenic concentration ≥ 25.6 ng/mL after seven days of induction may be beneficial for prognosis.

Objective：To analyze the clinical features of central nervous system involvement (CNS3) in pediatric anaplastic large cell lymphoma (ALCL) and evaluate the efficacy of CNCL-ALCL-2017 protocol for the treatment of CNS3. Methods：The clinical data of 215 pediatric ALCL patients ≤18 years old enrolled in the Chinese Children's Cancer Group (CNCL) between April 2017 and March 2023 were collected sequentially. All enrolled patients staging and CNS layering were according to the IPNHLSS staging system and treated with CNCL-ALCL-2017 protocol (modified BFM-ALCL99 protocol). The clinical features at diagnosis and treatment outcomes of CNS3 patients were analyzed. All patients were followed up until June 30, 2023. Data were collected using a unified information platform. Associations between patient characteristics were analyzed with Chi-squared or Fisher's exact tests. Eventfree survival (EFS) and overall survival (OS) curves were estimated according to the KaplanMeier method and compared by Logrank test. Furthermore, statistical analysis was performed using SPSS 22.0 software. P<0.05 was considered statistically significant. Results: Among the 215 ALCL pediatric patients, 17 (7.9%) had CNS3, including 13 males and 4 females with median age of 8.0 (range 1.0-14.0) years. In this patients, brain parenchyma and spinal cord involvement were found in 58.8% (10/17) patients on imaging, with space-occupying lesions in 7 cases and abnormal signals on MRI in 4 cases. Concurrent space-occupying lesions and abnormal signals on MRI was detected in 1 case. Cerebrospinal fluid (CSF) positivity was detected in 35.3% (6/17) patients, including 2 cases with positive ALK gene and 5 cases with positive flow cytometry, with 1 case positive for both. Cranial nerve deficits such as facial nerve palsy, visual or hearing impairment were observed in 23.5% (4/17) patients. Concurrent CSF, imaging and cranial nerve abnormalities were present in 5.9% (1/17), while two of this were present in 29.4% (5/17). Isolated CSF positivity without other abnormalities was detected in 23.5% (4/17). Pathological subtypes included common type (76.5%, 13/17), histiocyte-rich variant (5.9%, 1/17), small cell variant (5.9%, 1/17), others (11.8%, 2/17). Immunohistochemistry showed ALK + in 94.1% (16/17) and CD3 + in 76.5% (13/17). Concurrent ALK gene positivity in both peripheral blood and bone marrow was detected in 64.7% (11/17), with 58.8% (10/17) positive in both samples. The median follow-up of all patients was 35.4 months (range 0.5-74.9). All CNS3 patients had stage IV disease and were treated with regimen D (with 5 g/m 2 methotrexate). The 3-year OS was 94.3%, 98.2% and 93.3% for CNS1 (144, 67.0%), CNS2 (54, 25.1%) and CNS3 (17, 7.9%) patients, respectively; the 3-year EFS was 85.6%, 90.3% and 86.7%, respectively. No significant differences were found among the three groups. The 3-year OS and EFS for the whole cohort were 95.1% and 84.7%, respectively, also with no significant differences from the CNS3 group. Of the CNS3 patients, 1 was lost to follow-up after the first course, 1 died during treatment, and the interim CR rate was 75.0% (12/16). CSF conversion was achieved in 3/6 (50%) CSF-positive patients. 6.25% (1/16) patient had CSF ALK gene re-positivity during maintenance and persistent positivity despite additional ALK inhibitor alectinib and intrathecal therapy. In the CNS1 group, 2 cases were lost to follow-up and 4 cases died. The relapse rate was 11.4% (16/140), and the rate of central nervous system relapse was 2.1% (3/140). Additionally, the rate of CNS1 relapse was slightly higher but not statistically significantly different for CNS2. Conclusions: CNS involvement is relatively rare in pediatric ALCL. Detection rate of CNS3 can be improved by CSF flow cytometry and gene screening. The prognosis of CNS3 was significantly improved with CNCL-ALCL-2017 protocol, which may be related to the increased dose of methotrexate in the protocol. The short follow-up time and the small number of cases in this group may affect the results. Furthermore, CNS relapse rate of CNS2 was not markedly higher compared to CNS1. Keywords: Anaplastic large cell lymphoma; Pediatric; Central nervous system; Clinical features; Prognosis

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.

Mitochondrial dysfunction is crucial in the pathogenesis and drug resistance of pediatric T-cell acute lymphoblastic leukemia (T-ALL), a malignant hematological disorder with unrestrained proliferation of immature T-cells. Therefore, the primary objective of this study is to elucidate the role of mitochondrial dysfunction-related differentially expressed genes (MDRDEGs) in pediatric T-ALL and to establish a diagnostic model based on the MDRDEGs. We obtained datasets from GEO on pediatric T-ALL patients and healthy controls. A comprehensive list of 843 mitochondrial dysfunction-related genes (MDRGs) was compiled from GeneCards database and PubMed literature. Subsequently, we identified significant MDRDEGs, also, performed functional enrichment and analysis immune infiltration analysis. Additionally, A mitochondrial dysfunction-based signature was created to predict pediatric T-ALL. The mRNA-miRNA and mRNA-TF Regulatory Network were constructed, and the molecular distributions of key genes were calculated. There were 8029 differentially expressed genes (DEGs) in pediatric T-ALL compared to controls. Intersecting these DEGs with MDRGs yielded 284 MDRDEGs. Enrichment analyses revealed that these MDRDEGs were involved in oxidative stress response, cellular respiration, mitochondrial inner membrane composition, and protein complexes. GSEA and GSVA highlighted significant enrichment in NF-κB and JAK-STAT pathways. The intersection of LASSO regression and RF algorithms highlighted two pivotal genes: RNLS and ULK1. Validation dataset demonstrated our diagnostic model's high accuracy. In conclusion, this study systematically investigated MDRDEGs' roles in pediatric T-ALL and constructed an effective diagnostic model. The findings provided new potential biomarkers for early diagnosis and therapeutic targets for pediatric T-ALL, offering promising directions for future research.

T-cell lymphoblastic lymphoma (T-LBL) is an aggressive lymphoma that primarily affects children and young adults, and a comprehensive understanding of its molecular features is crucial for improving patient outcomes. In this study, 552 patients were included, with targeted next-generation sequencing of 262 lymphoma-associated genes performed on tumour samples from 119 patients. The associations between mutations and survival rates, as well as relapse and other clinical factors, were analysed. The results demonstrated that pleural effusion (PE) invasion was significantly associated with adverse event-free survival (EFS) and overall survival (OS) (p < 0.05). Additionally, we identified 92 genes with recurrent mutations, among which NOTCH1 (44%), FBXW7 (28%), PHF6 (11%), KRAS (10%) and NRAS (10%) were the most frequently altered. Patients with NOTCH1 mutations exhibited improved EFS and OS (p < 0.01), whereas those carrying CREBBP, PTEN and LYST mutations exhibited worse prognosis (p < 0.05). In conclusion, NOTCH1 mutations are associated with a favourable prognosis in paediatric T-LBL, while CREBBP, PTEN and LYST mutations, as well as PE invasion, are linked to poor prognosis. This study identifies key molecular and clinical factors in paediatric T-LBL progression, aiding high-risk patient identification and personalized treatment strategies.

Objective The ETV6RUNX1 fusion is the most common genetic abnormality in childhood B-cell acute lymphoblastic leukemia (B-ALL), yet nearly 50 % of relapses occur in patients initially classified as low-risk with this alteration. This study aimed to unravel the underlying pathways driving relapse in ETV6RUNX1 positive B-ALL. Methods Single-cell RNA sequencing (scRNA-seq) was performed on a cohort of four B-ALL patients with the ETV6RUNX1 fusion (three newly diagnosed and one relapsed case, selected from 25 patients). Results we discovered that relapsed samples exhibited a decline in T cell populations, an increase in CD8 Tex cells and B cells, and a higher proportion of malignant cells. Gene enrichment analysis demonstrated that IFN-γ response signaling pathways and inflammatory responses were significantly enriched in newly diagnosed samples. Conversely, the relapsed samples showed enrichment in the oxidative phosphorylation and glycolysis pathways. Additionally, analysis of cellular interactions revealed that malignant B cells could interact with T cells through LGALS9-HAVCR2, potentially leading to the exhaustion of effector T cells. Moreover, NPDC1, LEF1, and ERG exhibited higher activity levels in malignant B cells from relapsed patients, highlighting their roles in the progression and maintenance of leukemia. Conclusion In summary, our study provides valuable insights into the potential causes of relapse in B-ALL patients with ETV6RUNX1, providing a foundation for the identification of prospective therapeutic targets.

China-Net Childhood Lymphoma (CNCL) group B-NHL-2017 study is a prospective multi-center study in China, with the purpose of standardizing the diagnosis and treatment of childhood lymphoma, and improving the prognosis. From May 2017 to June 2023, 20 centers participated in the diffuse large B-cell lymphoma (DLBCL) study. The clinical data were analyzed to summarize the clinical characteristics, treatment response and outcome. The primary endpoint was 5-year event-free survival (EFS). The trial is registered with the Chinese Clinical Trial Registry (ChiCTR1800020067). A total of 138 children and adolescents were enrolled, including 101 males and 37 females. The median age of disease diagnosis was 9.0 years (range: 2.3–15.5 years). The range of follow-up time was 17 d–6.0 years. A total of 12 events occurred in this study, including 7 deaths. of which 4 patients died of disease and chemotherapy comorbidities (severe infection, septic shock, etc.), 1 died of disease progression (enlargement of the primary tumor and tumor metastasis), 1 died of recurrence, and 1 died of severe pneumonia in the third year after completing all chemotherapy courses. Recurrence occurred in 6 (4.3

Background:Blinatumomab, a bispecific T-cell engager targeting CD3+ and CD19+, promotes T cell-mediated cytotoxicity against B-cell precursor acute lymphoblastic leukemia (B-ALL). While its efficacy is established in relapsed/refractory (R/R) disease, its role as preemptive therapy for minimal residual disease (MRD)-positive patients or those experiencing chemotherapy delays remains undefined. Predictors of treatment failure also require further investigation. Methods:In this multicenter retrospective study, 105 patients who received blinatumomab were enrolled. Of these, 30 had R/R ALL, 21 were in complete remission (CR) with MRD positivity (CR-MRDpos), and 54 experienced chemotherapy delays. Eight patients received blinatumomab directly as reinduction therapy and 22 patients received burden-reduction chemotherapy prior to blinatumomab. In total, 11 children were in R/R status and 40 were in CR-MRDpos before treatment. Patients were subsequently bridged to stem cell transplantation, chimeric antigen receptor T-cell therapy (CAR-T), or protocol continuation. Treatment response was analyzed across CR-MRDpos, R/R, and CR with MRD negativity (CR-MRDneg). Immune reconstitution profiles (T-cell subsets, cytokine dynamics), cytogenetic markers, and clinical outcomes were assessed to identify predictors of treatment resistance. Results:The CR rate was 81.8% in R/R and 82.5% in CR-MRDpos patients (P = 1.000). Of 74 courses with CR-MRDneg, 73 remained MRD-negative during treatment. Univariate analysis revealed poor cytogenetics (P = 0.0001), CD19+ B-cell loss (P = 0.046), and BCR-ABL1 positivity (P = 0.002) as predictors of poor response. Cox regression analysis identified high MRD (P = 0.014), BCR/ABL1 (P = 0.065), and poor cytogenetics (P = 0.025) as independent risk factors. Blinatumomab significantly increased CD3+ T cells [0.96 (0.03-3.79) to 1.13 (0.26-7.74) ×109/L, P = 0.016], along with CD4+ [0.35 (0.01-1.39) to 0.47 (0.07-2.94) ×109/L] and CD8+ T cells [0.41 (0.01-2.39) to 0.56 (0.07-6.07) ×109/L] (P = 0.005 and P = 0.006, respectively).The 1-year event-free survival for CR-MRDneg, CR-MRDpos, and R/R patients was 97.8% ± 2.2%, 86.7% ± 6.2%, and 73.3% ± 8.1%, respectively (P = 0.001), while overall survival was 97.8% ± 2.2%, 100%, and 93.3% ± 4.6% (P = 0.029). Conclusions:Blinatumomab effectively clears MRD as preemptive therapy and serves as a bridging strategy during chemotherapy delays in pediatric B-ALL, while maintaining high response rates in R/R cases.

Burkitt lymphoma (BL) is a B-cell malignancy with a rapid doubling time, originating in follicular germinal centers. We aimed to explore the characteristics and prognosis of childhood Burkitt leukemia. A total of 124 children with Burkitt leukemia enrolled during the 6-year period of China Net Childhood Lymphoma- mature B-cell lymphoma 2017 regimen (CNCL-B-NHL-2017) were assessed. The median age at onset was 7 years (1–15 years), with a male-to-female ratio of 4.17:1. Of the total, 50.8

Objective: To investigate the clinical-pathology characteristics, risk factors, necessary for VBL maintenance therapy，through summarize the clinical data of 221 cases of pediatric Anaplastic Large Cell Lymphoma (ALCL), treated with CNCL-ALCL-2017 witch is modify from BFM-ALCL-99 (±vincristine maintenance therapy) in China Net Childhood Lymphoma (CNCL). Methods: Data were collected on 221 children with ALCL enrolled from CNCL at time between April 2017 to March 2023, including: numbers of cases enrolled in each single center, gender and age at the time of initial diagnosis, the first initial symptom, a delay diagnosis, the misdiagnosis disease , the site of involvement, the level of blood uric acid, the level of blood lactate dehydrogenase, the bone marrow and CNS status, tumor complication, complicated with HLH, staging and treatment subgroups, pathological subtypes, CD3 expression in tumor tissue, bone marrow and peripheral blood ALK gene expression at initial diagnosis (qPCR + FISH), and treatment outcomes, treatment strategy(vincristine maintenance or not), time from initial diagnose to relapse, second-line treatment regimen after relapse, and treatment outcomes after relapsed. Statistical analysis was conducted using SPSS 21.0 software. Results: 221 cases were from 22 hospitals in China. Male = 144 cases, female = 71 cases, age range from 1-16 years (median age 8.9 years), duration from initial symptoms onset to diagnosis was 0.3-11 months (median time 1.0 months), delayed diagnosis was present in 51(23%) children (45 children were misdiagnosed with infectious diseases). Pathological subtypes were: common sub type = 150(67.8%), small cell sub type = 19(8.5%), histiocytic variant subtype = 9(4%), ALK negative subtype = 12(5.4%).others = 31(14%). CD3 expression in tumor: negative = 119, positive = 91. ALK positive by qPCR in peripheral blood at the time of the initial diagnosis = 77, ALK positive by qPCR in bone marrow = 78, bulky disease= 21, mediastinal invasion = 84, CNS invasion = 17, skin invasion = 32. tumor related HLH = 25, normal LDH level at initial diagnosis = 133, 1-fold elevated = 45, 2-3-fold elevated = 39, 4-fold elevated = 2, >4-fold elevated = 2, stage I = 5, stage II = 24, stage III = 70, stage IV = 120 , leukemic stage = 2 . Grouping: group A = 1, group B = 21, group C = 191, group D = 8. Vincristine maintenance = 121. Median follow-up time was 35.4 months (0.5-74.9 months), OS at 3 years = 95.1±1.5% (95% CI = 90%-97.3%, Fig. 1), EFS at 3 years = 84.7±4.5% (95% CI = 79%-89.9%, Fig. 2), and there were a total of 23 patients with events, median time was7 months. There were 10 patients died, 5 of them quit to the treatment, median time was 5 months, and 13 patients who had an event but still alive after second line treatment. Univariate results of the 3 years EFS are detailed in Table 1, with statistically significant including (<0.05): tumor related HLH before treatment, LDH levels higher than 4 times normal and MDD positive at the beginning of the disease, and treated without VBL. The event patients are 23 cases ,the detailed in Table 2, which showed that the earlier the event occurs, the higher the mortality rate. Conclusion:Pediatric ALCL in China is mostly found in school-age boys, and it is easy to be diagnosed as infectious diseases at the time of initial diagnosis due to high fever and elevated CRP. 87% of patients were diagnosed as late stage or high-risk group. The application of the CNCL-ALCL-2017 protocol showed a 3-year OS 84.7% and 3-year EFS 95.1%, indicating that the efficacy was significantly better than that of various centers before the multi center cooperation. The overall survival time is significantly better than the event free survival time, indicating that most patients with progression and recurrence still have a chance of re remission after second line treatment. Adverse prognostic factors include a significant increase in LDH levels at initial diagnosis, initial onset of HLH, positive MDD before treatment, and no use of vinblastine maintenance therapy. Recurrent children: The median recurrence time is 7 months, and the prognosis of early progression and recurrence is worse than that of late recurrence. Key words: Anaplastic large cell lymphoma, Pediatric, Clinical-pathology features, Prognosis

BackgroundT-cell lymphoblastic lymphoma (T-LBL) is the second most common subtype of non-Hodgkin's lymphoma (NHL) in children and adolescents. Under current treatment, the event-free survival rate (EFS) is between 75% and 85%. The unified CNCL-LBL-2017 protocol was adopted for treatment in the China-Net Childhood Lymphoma Group（CNCL）in order to standardize the diagnosis and treatment of childhood lymphoma, and improve the prognosis. This study aimed to analyze the clinical features of pediatric T-LBL and evaluate the theraputic efficacy, explore the prognostic factors. Methods From May 2017 to June 2023, 548 newly diagnosed T-LBL patients aged ≤18 years from 29 centers in CNCL were enrolled in this study. According to clinical stage, prognostic genes and treatment response, the children were divided into low, intermediate and high risk groups, and stratified treatment was performed according to CNCL-LBL-2017 protocol modified from LBL-BFM95 trial, with follow-up until December 31, 2024. The therapies aimed at central nervous system (CNS), Cranial irradiation was omitted even for the patients with CNS involvement at the diagnosis. All patients received triple intrathecal injections, with stratified treatment based on CNS status. Patients with CNS2/CNS3 received more intrathecal injections. Results A total of 548 patients were included. The median age of disease diagnosis was 8.0 years (range:1.0-16.0 years. There were 413 (75.4%) males and 135 (24.6%) females. The disease course of 434 patients(79.2%) was less than 30 days. Clinical staging: 1 case(0.2%) in stage Ⅰ, 3 cases(0.5%) in stage Ⅱ , 153 cases (27.9%) cases in stage Ⅲ and 391 cases(71.3%) in stage Ⅳ. 426 cases（77.7%）presented with anterior mediastinal mass, 386（70.4%）bone marrow involvement, 54（9.9%）CNS involvement. Median serum LDH value was 632 IU/L (range 108-35,645); 198 patients(36.1%) had a LDH value more than 1,000 IU/L.148 cases (27.0%) of the children had symptoms of airway obstruction at diagnosis, and 137 cases (25.0%) were accompanied by superior vena cava syndrome (SVCS). 49 cases (8.9%) were complicated with tumor lysis syndrome (TLS) during prednisone pretreatment. There were 1 case (0.2%), 164 cases (29.9%), and 383 cases (69.9%) in the low, intermediate, and high-risk groups, respectively. The follow-up time was 44.5 (0.8, 93.9) months. The 5-year EFS rates and 5-year overall survival(OS) were 77.1±1.9% and 84.2±1.6%, respectively. The 5-year EFS rates of low, intermediate and high risk groups were 100.0%, 77.6±3.3% and 77.6±2.3%, respectively. Recurrence/progression occurred in 98 cases (31 BM relapses, 18 CNS, 25 primary sites, 2 testicular, 22 multisystem recurrence), recurrence rate 17.9%, and the recurrence time was 11.5 (2.1, 75.6) months, in which 72 cases died and 26 cases survived. The recurrence rate of CNS is 3.3%. All patients experienced grade 3-4 hematological toxicity. Infection-related death occurred in 21 cases (3.8%). Eighty-four patients with high-risk factors or relapsed/refractory conditions received allogeneic hematopoietic stem cell transplantation in this study. Based on Cox regression analysis, the failure to achieve complete remission at the end of induction (mid-term evaluation) (HR=8.528, 95%CI: 2.832-25.237, P=0.001) was the only risk factors for EFS rate. Conclusion T-LBL in childhood and adolescence is highly aggressive and liable to relapse in the early stage of treatment. CNCL-2017-LBL protocol got a certain efficacy close to the results of international studies. High-intensity chemotherapy has improved the therapeutic effect for patients in the high-risk group. CNS relapse incidence rate didn't increase without cranial irradiation.

Introduction: Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a major subtype of pediatric non-Hodgkin lymphoma. NPM1::ALK is the most common fusion in Chinese pediatric ALK-positive ALCL patients. However, the prognostic implications of variant ALK fusions and genetic profiles in Chinese pediatric patients with ALK-positive ALCL has not been fully characterized, hindering risk-adapted treatment strategies. Amis: This study aimed to explore the molecular variation characteristics of Chinese pediatric ALK-positive ALCL patients, including the distribution of fusion partner genes and mutation genes, as well as their relationship with prognosis. The findings will provide a basis for clinical prognosis assessment and personalized treatment. Methods: We analyzed 323 pediatric patients with ALK-positive ALCL (≤16 years) from the China Network of Childhood Lymphoma (CNCL). ALK-fusion status was determined by quantitative RT-PCR in 323 patients, and targeted next-generation sequencing of 262 lymphoma-related genes was performed in 50 patients. Molecular-clinical correlations were evaluated for survival and relapse outcomes. The median follow-up time was 36.8 months (95% CI: 31.6-40.8). Results: Of 323 pediatric ALK-positive ALCL patients with fusion data, 275 (85.1%) had ALK fusions. The majority (n=247, 89.8%) carried NPM1::ALK fusions, while 28 (10.2%) had non-NPM1::ALK fusions. Among the variant ALK-partner genes, we detected TPM3 (n = 7; 25% of variant fusions), TPM4, TRAF1, ATIC and CLTC (each n = 3; 11%), EEF1G, KIF5B and MYH9 (each n = 2; 7%), and EVI1, SATB1 and TXLNA (each n = 1; 4%). Univariate-Cox regression analysis revealed significantly poor event-free survival (EFS) in patients with non-NPM1::ALK fusions (log-rank p<0.001; median EFS: 30.5 months, 95% CI: 17.5–NA). The 3-year EFS rate was 28.9% in the non-NPM1::ALK group compared with 70.7% in the NPM1::ALK group. No significant difference in overall survival (OS) was observed. Among 50 patients with mutation data, 36 (72%) carried somatic mutations. A total of 39 mutated genes were identified, with TP53 (26%), STAG2 (12%), KMT2A (6%), PRDM1 (6%), and TET2 (6%) being most frequent. Other recurrently mutated genes included KIT, KMT2D, NF1, PCLO, USH2A, and VCAN. Univariate-Cox regression analysis showed that compared with those without TP53 mutations, the patients with TP53 mutationshad significantly poorer EFS and OS (EFS: log-rank p=0.03, median EFS=11.1 months [95%CI: 7.17-NA], 3-year EFS: 27.0% [95%CI: 8.43-86.5%], OS: log-rank p=0.0025, 3-year OS: 66.7% [95%CI: 37.9-100%]). Further analysis revealed that among patients with NPM1::ALK fusions, TP53 mutations were significantly associated with inferior outcomes, whereas no TP53-mutated cases were identified in the non-NPM1::ALK fusion subgroup. No significant co-occurrence or mutual exclusivity was observed between fusion types and mutations. Conclusions: In Chinese pediatric patients with ALK-positive ALCL, the NPM1::ALK fusion represents the most common genetic alteration, while variant ALK-partners account for approximately 10% of cases. Non-NPM1::ALK fusion correlated with unfavorable outcomes in this cohort. Additionally, TP53 mutations, which were observed in 26% of patients, were associated with poor prognosis. The mechanistic interplay between these molecular aberrations and clinical outcomes warrants further investigation. (Yang Li & Jing Yang; Qinlong Zheng & Yonghong Zhang contributed equally).

PurposeTo retrospectively evaluate the clinical features and prognostic factors of pediatric LCH patients treated in a single center of China.MethodsPediatric LCH cases were treated following the SD-LCH protocol at the Affiliated Provincial Hospital of Shandong First Medical University in Jinan, China. An analysis was conducted on 82 recently identified LCH cases to retrospectively evaluate the initial symptoms, therapeutic alternatives, and extended results. Follow-ups were conducted until July 31, 2023.ResultsThe median age at diagnosis was 2 (0.25–12) years. 42 (51.2%) were SS-LCH, and 40 (48.8%) were MS-LCH. The most common organ involved was bone (82.9%). Over the 16-year follow-up period, the 5-year EFS and OS rates were 75.2 ± 5% and 90.9 ± 3.3%, respectively. The cumulative reactivation rate was 23.2%. The 5-year EFS rate in SS-LCH and MS-LCH patients were 90.2 ± 4.6% and 58.8 ± 8.3%, and the 5-year OS rate in SS-LCH and MS-LCH patients were 90.2 ± 4.6% and 81.2 ± 6.5%, respectively. The 5-year OS and EFS rate in RO+ LCH and RO− LCH patients were 79.5 ± 7.5%, 53.8 ± 9.6% and 87.5 ± 11.7%, 76.2 ± 14.8%, insignificantly. Multivariate Cox regression showed that liver involvement predicted poor EFS and hematological system involvement was an independent prognostic factor for OS. Detection of the BRAFV600E mutation and targeted therapy significantly improved the prognosis post-2017.ConclusionLiver or hematological system involvement indicates a poor prognosis, and the SD-LCH protocol improves prognosis for pediatric LCH patients.

Objective:A child's cancer diagnosis is a significant family event, and there is a need to explore factors that influence the quality of life of children with cancer from family-based perspectives. This study aimed to explore the interrelationships between parental burnout, sibling relationship quality, and quality of life in children with cancer. Methods:This cross-sectional study enrolled 218 children with cancer and their parents in three tertiary hospitals in Shandong Province using convenience sampling. Children completed the Chinese version of the Pediatric Quality of Life Inventory 4.0, while their parents completed the Parental Perceptions of Children's Sibling Relationship Quality Questionnaire and Maslach Burnout Inventory, and provided their own sociodemographic information, as well as their children's sociodemographic and clinical characteristics. Network analysis was employed to examine the relationships between variables. Results:In the overall network, social functioning in children with cancer exhibited the highest strength (r s ​= ​1.03), while warmth in sibling relationship quality showed the highest bridge strength (r bs ​= ​0.42). Social functioning was positively associated with warmth in sibling relationship quality (r ​= ​0.15), and negatively associated with personal achievement (r ​= ​-0.13) and depersonalization (r ​= ​-0.09) in parental burnout. Emotional functioning was negatively associated with emotional exhaustion in parental burnout (r ​= ​-0.10) and jealousy in sibling relationship quality (r ​= ​-0.10). Conclusions:There are significant interrelationships between the network structure of family related variables and quality of life in children with cancer. These findings offer guidance for healthcare professionals focusing on family-based interventions to improve the quality of life of children with cancer.