BACKGROUND:Doxorubicin, an anthracycline chemotherapeutic agent, is widely used in diffuse large B‑cell lymphoma (DLBCL) treatment, yet its clinical efficacy is often compromised by drug resistance. Protein arginine methyltransferase 7 (PRMT7) is a methyltransferase implicated in tumourigenesis and cancer progression. However, its precise role and underlying mechanisms in DLBCL progression and doxorubicin resistance remain unclear. METHODS:We analysed PRMT7 expression in DLBCL cell lines and patient specimens using bioinformatic databases, western blotting, reverse Transcription Polymerase Chain Reactionand immunohistochemistry. Functional studies were performed in DLBCL cell lines through CRISPR/Cas9‑mediated knockout and overexpression systems, combined with in vitro assays for proliferation, apoptosis and doxorubicin sensitivity, as well as in vivo xenograft models. Mechanistically, co‑immunoprecipitation, arginine methylation assays and immunofluorescence were employed to characterise the PRMT7-Forkhead box K (FOXK)1/2-Dishevelled Segment Polarity Protein 2 (DVL2) axis and its modulation of Wnt/ (beta) β‑catenin signalling. In addition, we designed and evaluated FOXK‑methylation‑competitive inhibitory peptides for their capacity to sensitise DLBCL cells to doxorubicin. RESULTS:Our study revealed that PRMT7 is upregulated in DLBCL and promotes both tumour proliferation and doxorubicin resistance. Conversely, knockdown of PRMT7 inhibited DLBCL cell proliferation and enhanced sensitivity to doxorubicin. Mechanistically, PRMT7 catalyses arginine methylation of FOXK1 at arginine (R) 191 and FOXK2 at R144, which markedly increases their binding affinity for DVL2 and facilitates DVL2 nuclear translocation. This event leads to constitutive activation of the Wnt/β‑catenin signalling pathway. Importantly, we developed a FOXK‑derived peptide that competitively inhibits FOXK methylation, suppresses Wnt/β‑catenin signalling and significantly potentiates the antitumour efficacy of doxorubicin in DLBCL. CONCLUSION:Our findings indicate that the PRMT7/FOXK/DVL2/Wnt-β-catenin axis serves as a novel driver of DLBCL progression and doxorubicin resistance. Targeting the PRMT7-FOXK methylation interface may offer a potential therapeutic approach for overcoming doxorubicin resistance in DLBCL, although further validation in clinical settings is warranted. KEY POINTS:Upregulated PRMT7 drives DLBCL progression and doxorubicin resistance PRMT7 methylates FOXK1 at arginine 191 and FOXK2 at arginine 144 FOXK1/2 methylation enhances interaction with DVL2 and promotes nuclear translocation FOXK1/2 methylation dactivate Wnt/ß-catenin signaling through DVL2 nuclear entry A novel peptide inhibitory blocks FOXK1/2 methylation and restores doxorubicin sensitivity.

IntroductionTesticular relapse constitutes one of the most frequent extramedullary recurrences in pediatric acute lymphoblastic leukemia (ALL), yet its clinical management remains incompletely characterized.MethodsThis study assessed treatment outcomes and long-term survival in children with testicular relapse following initial therapy under the CCCG-ALL-2015 study (ChiCTR-IPR-14005706, http://www.chictr.org.cn). In total, 66 patients from 13 medical centers were retrospectively analyzed. Clinical characteristics and survival outcomes were compared across salvage treatment modalities.ResultsThe median interval from initial diagnosis to testicular relapse was 37 months. Among 59 patients who received post-relapse therapy, the 2-year overall survival (OS) rate was 86.1% after a median follow-up of 33 months. Patients treated with chimeric antigen receptor T-cell (CAR-T) therapy showed a 2-year OS of 90.7%, compared to 81.7% in those managed with conventional regimens, such as chemotherapy, orchiectomy, or hematopoietic stem-cell transplantation (P > 0.05). Among 37 children with isolated testicular relapse, 18 underwent CAR-T therapy and 10 underwent orchiectomy, achieving 2-year OS rates of 92.3% and 100%, respectively (P > 0.05).DiscussionTesticular relapse typically emerged approximately 3 years after initial diagnosis. CAR-T therapy proved to be both safe and effective, providing survival comparable to conventional regimens and offering potential advantages in preserving life quality among long-term survivors.

Over the past several decades, cure rates for paediatric hematologic malignancies have improved due to advances in cancer therapy. However, numerous obstacles limit the therapeutic efficacy of paediatric solid tumours, including the tumour's immunosuppressive microenvironment and the lack of specific tumour antigens for targeted therapy. Cancer vaccines, a form of immunotherapy, have been under development for more than half a century. Advances in immunology, materials science, sequencing technologies and bioinformatics have revolutionised cancer vaccine development, achieving substantial success in the prevention and treatment of solid tumours. Despite these achievements, the application of cancer vaccines developed for adults is not fully transferable to paediatric solid tumours because of differences in immune status and metabolic capacity. In clinical practice, most solid tumour vaccines designed for adults are applied directly to paediatric patients without modifications tailored to the unique features of the paediatric immune system. Limited attention has been given to designing cancer vaccines with improved efficacy and reduced toxicity for children and infants. This review discusses paediatric solid tumour vaccines from the immune system against tumour to different antigen types of cancer vaccines, illustrating the unique cancer-immunity cycle of young people and some potential strategies for vaccine modification. Additionally, it discusses the application of paediatric solid tumour vaccines through clinical trial data for conditions such as neuroblastoma, brain tumours and sarcomas. Challenges and potential solutions for enhancing vaccine efficacy, minimising side effects and broadening clinical applications are also addressed.

ObjectiveThe high toxicity of current therapies and frequent relapse in mature B-cell non-Hodgkin lymphomas (B-NHLs) reveal a substantial unmet clinical need for more effective targeted treatment strategies. To address this gap, Gene Set Enrichment Analysis (GSEA) of B-NHL datasets was conducted, uncovering marked enrichment of E2F transcription factors and their target genes. Despite the central role of E2F signaling in cell cycle control and oncogenesis, its contribution to pediatric B-NHLs has not been systematically characterized. Accordingly, we performed a comprehensive analysis of E2F signaling and its downstream targets to identify potential therapeutic and prognostic biomarkers in pediatric B-NHLs.MethodsThe datasets used for this analysis were obtained from the Gene Expression Omnibus (GEO) database, and mRNA and protein expression levels were further validated via data from The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). Key bioinformatics findings were validated via quantitative PCR (qPCR) and cell proliferation assays. Survival analysis was conducted to evaluate the associations between gene expression levels and the prognosis of B-NHL patients. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA were employed to predict gene functions and associated pathways.ResultsChildhood B-NHLs were markedly enriched for E2F gene set. The identified overlapping differentially expressed genes (DEGs) were linked to cell cycle regulation, DNA replication, and proliferative activity. E2F1 and hub genes such as POLD1, LIG1, MCM3, MCM6, and PCNA were markedly overexpressed in B-cell lymphoma. These genes demonstrated strong discriminatory potential as disease-associated signaling molecules. Moreover, the expression of POLD1 was closely associated with the proliferative capacity of B-NHLs.ConclusionE2Fs and their downstream target genes are significantly overexpressed in pediatric B-NHLs, driving tumor cell proliferation. These molecules may serve as biomarkers for therapeutic stratification, prognosis, and disease monitoring in pediatric B-NHLs.

Background Infections in immunocompromised pediatric hematology-oncology patients present a major challenge. This study utilized pathogen NGS (metagenomic next generation sequencing (mNGS) / targeted next generation sequencing (tNGS)) to characterize the microbial spectrum in this population, thereby enhancing detection and enabling targeted antimicrobial therapy. Methods This retrospective study enrolled pediatric patients with hematologic malignancies. The analysis employed descriptive statistics for pathogen profiles and comparative statistics to assess variations by clinical stage and outcome, and to evaluate NGS against traditional pathogen detection (TPD). Results This study included 72 children with a median age of 8 years. A total of 83 NGS tests were performed. Microbial organisms were detected by NGS in 70 samples, yielding 26 bacterial, 14 viral, and 12 fungal species. No statistically significant difference in NGS positivity was observed between the non-agranulocytosis (A1) and agranulocytosis (A2) groups ( P = 0.374). Escherichia coli (n = 5), Candida albicans (n = 5), and Human beta herpesvirus 5 (CMV, n = 21) were the most prevalent bacterial, fungal, and viral pathogens, respectively. Analysis of blood samples revealed that Escherichia coli, Aspergillus flavus , and Human gamma herpesvirus 4 (EBV) were the predominant bacterial, fungal, and viral pathogens, respectively. Statistical comparison revealed comparable rates of viremia between groups A1 and A2 ( P >0.999), whereas group A2 had a greater risk of bloodstream infection ( P = 0.023). Among the 61 blood samples, 49 (80.3%) were positive by mNGS, whereas only 7 were positive by TPD)(all of which were also mNGS-positive). All 11 pulmonary samples tested by tNGS were positive, while TPD was positive in only 1 specimen. tNGS identified Pneumocystis jirovecii in 3 samples, all of which were missed by TPD. NGS-guided antibiotic adjustment in 53.5% of patients with bacterial/fungal infections led to a favorable outcome, with an 88.4% cure rate after a median treatment of 12.1 days. Conclusions This study identified predominant pathogens ( Escherichia coli . Candida albicans s, CMV) and demonstrated that NGS, which is agranulocytosis, enhances detection of bacterial/fungal infections, enabling precision antimicrobial therapy in pediatric chemotherapy patients. Clinical trial number: not applicable. Trial registration: not applicable.

Purpose:Cytomegalovirus (CMV) infection represents a severe complication following hematopoietic cell transplantation (HCT), resulting in high mortality. The prevention of CMV reactivation is crucial for enhancing patient prognosis post-HCT. Letermovir prophylaxis has effectively reduced the incidence of clinically significant CMV infection (csCMVi) in adult HCT recipients. However, clinical data in pediatric patients remain limited. Patients and methods:We included 106 children who underwent HCT at our hospital between March 2019 and July 2024. The patients were grouped based on whether or not they received letermovir prophylaxis. By analyzing their general characteristics and laboratory findings, exploring the risk factors of csCMVi, and assessing the efficacy and safety of letermovir in pediatric patients. Results:Among the 106 patients, all patients were at high risk for CMV reactivation. Forty-four received letermovir prophylaxis, while 62 did not. CsCMVi occurred in 45 patients, with a significantly lower incidence in the letermovir group compared to the control group (5 [11.3%] vs 40 [64.5%], p < 0.001). Umbilical cord blood (UCB) was used in 7 patients (15.9%) in the letermovir group and in 1 patient in the control group (p < 0.05). There was no statistically significant difference in all-cause mortality between the two groups. Grade II-IV GvHD and the use of letermovir were associated with csCMVi, with letermovir identified as the only independent preventive factor for csCMVi during the first 100 days post-HCT, especially in patients with 4-5 risk factors of csCMVi. In patients with aplastic anemia, the incidence of csCMVi was notably lower in those who received letermovir prophylaxis. No patients in the study withdrew from treatment due to adverse reactions. Conclusion:Letermovir is both effective and safe for CMV prophylaxis in pediatric patients following HCT, especially in patients with more risk factors of csCMVi. Grade II-IV GvHD increases the risk of csCMVi, while letermovir prophylaxis reduces the risk.

Purpose:Pediatric Rosai-Dorfman disease (RDD) is extremely rare, and the current treatment plan is not unified. We hope that our study provides new ideas for the clinical treatment of RDD. Methods:We report a case in which RDD was successfully treated with prednisone and vincristine, resulting in regression of enlarged lymph nodes. In this study, informed consent forms were obtained from participants for their involvement in the research and publication of relevant case details. Moreover, this study aimed to conceal personal patient information. Results:The child underwent two pathological examinations before a definitive diagnosis was made. Percutaneous fine-needle aspiration biopsy was performed on his first admission, and pathological examination showed a purulent granulomatous reaction under a microscope; however, antibiotic treatment was ineffective. The second pathological biopsy performed at the time of surgery showed RDD. After treatment with vincristine and prednisone, the neck mass significantly shrank and did not increase in size after the treatment was stopped. The patient remains under follow-up. Conclusions:Sufficient pathological tissue samples were obtained via surgical biopsy to diagnose RDD. Treatment with chemotherapy, including prednisone and vincristine, can induce remission of RDD.

Pediatric pancreatic acinar cell carcinoma (PACC) is an exceptionally rare and poorly understood malignancy with a challenging prognosis. Its clinical presentation is often atypical, and standardized treatment guidelines are currently unavailable. While genetic alterations in adult PACC have been studied to some extent, knowledge of genetic abnormalities in pediatric cases remains limited. We report a case of pediatric PACC in a 7-year-old male presenting with a large, non-tender abdominal mass (11 cm x 11 cm) on the right side. Pathological and imaging evidence confirmed the diagnosis of PACC, with no lymph node infiltration or distant metastasis. Comprehensive genomic profiling by next-generation sequencing identified a non-canonical BRAF fusion with KMT2C at the DNA level and a classic SND1-BRAF fusion at the RNA level. The patient underwent surgical resection through a Whipple operation followed by six cycles of mFOLIRINOX chemotherapy and radiation therapy, achieving a favorable outcome up to now. Next-generation sequencing has demonstrated significant value in identifying genetic fusions in pediatric PACC. In our case report, we identified both the classical SND1-BRAF fusion, commonly associated with PACC, and a previously unreported nonclassical BRAF-KMT2C fusion. These findings underscore the critical role of BRAF alterations as key drivers of oncogenesis in PACC. A multidisciplinary treatment strategy integrating surgery, chemotherapy, and radiation therapy offers a promising precedent for improving therapeutic outcomes and prolonging survival in pediatric PACC cases.

Table S2. Response outcomes of induction therapy

The evolving molecular portrait of acute myeloid leukemia (AML) has exposed previously unrecognized cell death programs that fuel disease progression and treatment resistance—uncovering untapped therapeutic potential. Recent work has uncovered disulfidptosis—a novel form of programmed cell death (PDC) triggered by glucose deprivation in SLC7A11-high AML cells—as a potential therapeutic vulnerability. However, disulfidptosis in pediatric AML (pAML) remains largely unexplored, with no comprehensive studies assessing its biological significance or clinical prognostic value. Here, we systematically characterize disulfidptosis in pediatric AML through multi-omics integration. Using ssGSEA, we quantified PDC patterns across bulk and single-cell transcriptomes, revealing distinct molecular subtypes via unsupervised clustering. Machine learning deciphered the biological networks underlying disulfidptosis, while in vitro experiments were performed to further validate. In this study, we demonstrated that elevated disulfidptosis scores were associated with poor prognosis and a hypermetabolic state. Notably, patients carrying different driver mutations exhibited distinct levels of disulfidptosis susceptibility. Through in vitro experiments utilizing both cell lines and primary patient-derived cells, we found that elevated expression of SLC7A11, a key regulator of disulfidptosis, correlated with chemoresistance. Furthermore, disulfidptosis signatures effectively stratified risk subgroups in pAML, revealing a novel subtype, DSP3, characterized by prominent disulfidptosis features, an immune-desert tumor microenvironment, and an unfavorable prognosis. Additionally, our in vitro experiments identified the GLUT1 inhibitor STF-31 and the mitochondrial-targeted agent darinaparsin as potential therapeutic options for DSP3 patients, and combining with conventional chemotherapy exhibited a synergistic anti-tumor effect. In summary, this study employed multi-omics analysis to examine the characteristics of pAML in the context of disulfidptosis, identifying a novel disulfidptosis-related subtype, aiming to provide new insights for future studies on optimizing traditional regimen based on pAML pathogenesis.

PURPOSE:Venetoclax (VEN) has shown excellent activity in eliminating acute myeloid leukemia (AML) blasts in preclinical and clinical trials, but clinical data in pediatric newly diagnosed AML (ND-AML) remain limited. We evaluated VEN plus modified-intensity idarubicin and cytarabine chemotherapy (VIA) in childhood ND-AML. PATIENTS AND METHODS:In an open-label, single-arm, multicenter prospective clinical trial, 65 pediatric patients with ND-AML received VIA induction. Consolidation was guided on response to induction and individualized risk stratification. Primary end point was complete remission and measurable residual disease (MRD) response rates. RESULTS:After induction cycle 1, complete remission and MRD negativity was 90.8% and 78.5%, increasing to 96.8% and 87.3% following induction cycle 2. A total of 28 (43.2%) patients underwent hematopoietic stem cell transplantation without engraftment failure. Patients with core-binding factor (CBF) AML [t(8;21) and inv(16)/t(16;16)] achieved a favorable response rate, but the median log10 reduction of transcript levels was suboptimal [-1.7 (cycle 1) and -2.6 (cycle 2) for RUNX1::RUNX1T1 and -2.3 and -2.5 for CBFB::MYH11]. Disease relapse was frequently observed in KIT mutation, RUNX1::RUNX1T1, and CBFB::MYH11. The most common grade 3 to 4 toxicities were hematologic toxicities and febrile neutropenia. No treatment-related deaths occurred. With a median follow-up of 15.7 months, the estimated 12-month overall survival and event-free survival was 92.3% (95% confidence interval, 86.0-99.8) and 79.1% (95% confidence interval, 69.6-90.0). MRD negativity after cycle 1 correlated with superior long-term survival (P < 0.001). CONCLUSIONS:The VIA regimen is highly effective and relatively safe in children with ND-AML, with deep remission and favorable survival outcomes observed.

OBJECTIVES:To explore the factors related to prognosis and treatment failure in children with acute lymphoblastic leukemia (ALL). METHODS:A retrospective study was conducted to collect and analyze clinical data of ALL children admitted to the Department of Pediatric Hematology at Tongji Hospital, Huazhong University of Science and Technology, from January 2012 to December 2019, with follow-up until June 2024. RESULTS:A total of 341 children with ALL were included. Among the 69 children with treatment failure, 55 (80%) experienced relapse, while 14 (20%) had non-relapse-related deaths, and no secondary tumors were observed. Initial WBC count ≥50×109/L, positive minimal residual disease, and severe adverse events were identified as independent risk factors for treatment failure (P<0.05). Among the 55 relapsed patients, early relapses were predominant (36%), and the primary site of relapse was the bone marrow (56%). Immunophenotyping (P=0.009), initial WBC count (P=0.011), and fusion genes (P=0.040) were associated with the timing of relapse. High-risk status, T-cell ALL, relapse, and severe adverse events were independent risk factors affecting long-term survival (P<0.05). CONCLUSIONS:The prognosis of children with ALL is related to risk stratification, immunophenotyping, relapse status, and occurrence of severe adverse events. Among these factors, relapse is the primary cause of treatment failure. Actively preventing relapse may reduce the treatment failure rate and improve long-term survival.

BACKGROUND:Neuroblastoma (NB) with MYCN amplification is strongly correlated with high-risk stratification and poor prognosis. However, the underlying mechanisms remain incompletely understood. Elucidating these pathways is critical for advancing personalized treatments for MYCN-driven NB. METHODS:We performed single-cell transcriptomic analysis comparing NB samples with and without MYCN. Key genes were then identified using machine learning based random survival forest (RSF) and nomogram analyses. The influence of key genes on immune infiltration and molecular mechanisms driving NB progression were further investigated. Finally, we visualized the expression levels and global function of these genes in single-cell datasets and validated their expression in patient samples through RT-qPCR. RESULTS:Single-cell transcriptome analysis of GSE218450 identified marker genes specific to NB cells. RSF and nomogram analyses revealed that overexpression of CKB, PCSK1N, OTUB1, and VGF is associated with poor prognosis, whereas upregulation of NTRK3 indicates a favorable prognosis. These genes are significantly associated with immune cell infiltration and play an important role in modulating the immune microenvironment. Pathway analysis further showed that these genes influence critical signaling pathways, including the Wnt pathway, and interact with tumor-related genes. Additionally, we confirmed that CKB and PCSK1N are positively correlated with MYCN in NB cell lines and are significantly overexpressed in MYCN-amplified NB patients. CONCLUSIONS:Our results provide molecular insights into the transcriptional changes associated with MYCN amplification in NB. In particular, the identification of CKB and PCSK1N suggests their potential role in driving tumor progression, making them promising targets for novel treatments in MYCN-driven NB.

Background: Acute lymphoblastic leukemia (ALL) is the predominant malignancy in pediatric patients. As a crucial constituent of ALL chemotherapy, l-asparaginase is recognized as an integral element of treatment with a threshold concentration of 0.1 IU/mL used in treatment protocols. This study presents a novel liquid chromatography-tandem mass spectrometry method for evaluating plasma l-asparaginase activity in pediatric patients with ALL undergoing pegaspargase therapy. Methods: Initially, an enzyme incubation was conducted using 20 mu L of plasma and 100 mu L of l-asparagine (0.1 mol/L) at 37 degrees C for 15 minutes. The reaction was stopped by adding sulfosalicylic acid and methanol. After the addition of isotope internal standard l-aspartic C-13(4) acid, subsequent centrifugation, and dilution, the plasma samples underwent analysis by liquid chromatography-tandem mass spectrometry on a hydrophilic interaction liquid chromatography analytical column. A flow rate of 0.3 mL/min was used during isocratic elution using a mobile phase consisting of methanol-water (95: 5, vol/vol) with 0.2% formic acid within a 5-minute run. Results: The calibration curves exhibited excellent linearity ranging from 0.1 to 15 IU/mL, with determination coefficients (r(2)) exceeding 0.99. The precision and accuracy ranged from 1% to 7% and from 93% to 110%, respectively. The relative recovery fell within the range of 98%-100%, and the internal standard-normalized matrix effect ranged from 95% to 101%. The stability was satisfactory across various conditions. Conclusions: This method was fully validated and successfully applied to quantify l-asparaginase activity in plasma samples of 15 children with ALL, enabling the monitoring of l-asparaginase activity with mass spectrometry.

A retrospective analysis was conducted on the clinical course of two children with PICALM-MLLT10-positive acute leukemia treated at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between July 2021 and July 2023. The patients were diagnosed with acute T-lymphoblastic leukemia with central nervous system involvement and high-risk acute myeloid leukemia, respectively. Both achieved bone marrow complete remission after conventional chemotherapy combined with venetoclax. Following conversion to molecular negativity, they underwent sequential allogeneic hematopoietic stem cell transplantation. At the latest follow-up, both patients were alive and in good clinical condition. These observations suggest that proceeding to hematopoietic stem cell transplantation after venetoclax-based chemotherapy may improve the long-term survival of children with PICALM-MLLT10-positive leukemia.

Table S1. Study Representativeness Table

Background: The detection of mutations from circulating tumor DNA (ctDNA) represents a promising enrichment technique. In this retrospective study, the significance of ctDNA and imaging in Langerhans cell histiocytosis (LCH) monitoring was first examined, and the broader role of ctDNA in monitoring LCH was additionally explored. Methods: First, data visualization and survival analysis models were used to generalize the concordance between cfBRAFV600E molecular response and radiographic response on clinical outcomes. Next, the molecular response of cfBRAFV600E was observed from a dynamic perspective. A comparative analysis was then conducted between cfBRAFV600E and ltBRAFV600E status, examining their relationship to clinical manifestations and prognosis of LCH. Results: Eventually, 119 participants were enrolled in this trial between 2019 and 2023. Progression-free survival (PFS) was significantly shorter in patients with both radiologic and cfDNA molecular progression (17.67 versus 24.67 months, p < 0.05) compared to those without. A critical cfBRAFV600E value of 0.03% has been determined for the first time. Both cfBRAFV600E and ltBRAFV600E mutations were associated with a higher proportion of children under 3 years of age, skin and spleen involvement, and a lower 3-year PFS rate. In contrast to ltBRAFV600E, cfBRAFV600E was linked to a higher proportion of risk organ invasion LCH (52% vs. 27.9%, p < 0.05) and a better therapeutic response at the sixth week (24% vs. 4.7%, p < 0.05). Furthermore, in patients with risk organ invasion-LCH and multisystem-LCH subtypes, cfBRAFV600E was associated with a significantly lower 3-year PFS. Conclusions: In summary, these findings enhanced and supplemented the implications of ctDNA and imaging analysis application in children with LCH.

Background: PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB-positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease. Methods: This multicenter, retrospective study included 6457 pediatric patients with newly diagnosed PDGFRB fusion ALL according to the CCCG-ALL-2015 and CCCG-ALL-2020 protocols from April 2015 to April 2022 in 20 hospitals in China. Of these patients, 3451 were screened for PDGFRB fusions. Results: Pediatric PDGFRB-positive ALL accounted for only 0.8% of the 3451 cases tested for PDGFRB. These patients included 21 males and seven females and 24 B-ALL and 4 T-ALL; the median age was 10 years; and the median leukocyte count was 29.8 x 10(9)/L at baseline. Only one patient had eosinophilia. Three patients had an IKZF1 deletion, three had chromosome 5q31-33 abnormalities, and one suffered from a complex karyotype. The 3-year event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were 33.1%, 65.5%, and 32.1%, respectively, with a median follow-up of 25.5 months. Twenty patients were treated with chemotherapy plus tyrosine-kinase inhibitors (TKIs) and eight were treated without TKI. Complete remission (CR) rates of them were 90.0% and 63.6%, respectively, but no differences in EFS, OS, or CIR. Univariate analyses showed patients with IKZF1 deletion or measurable residual disease (MRD) >= 0.01% after induction had inferior outcomes (p < .05). Conclusions: Pediatric PDGFRB-positive ALL has a poor outcome associated with high-risk features. Chemotherapy plus TKIs can improve the CR rate, providing an opportunity for lower MRD levels and transplantation. MRD >= 0.01% was a powerful adverse prognostic factor, and stratified treatment based on MRD may improve survival for these patients.

目的 观察艾迪注射液联合可穿戴设备肺康复训练治疗晚期非小细胞肺癌化疗患者临床疗效.方法 将我院收治的100例晚期非小细胞肺癌化疗患者随机分为观察组与对照组各50例.对照组患者给予可穿戴设备肺康复训练治疗,观察组在对照组治疗基础上加用艾迪注射液治疗.比较两组1 s用力呼气容积(FEV1)、用力肺活量(FVC)、最大通气量(MVV)、6 min步行试验(6MWT)、Borg呼吸困难评分、Piper癌因性疲乏自评修正量表(RPFS)评分的差异.结果 治疗后,两组FEV1、FVC、MVV均增加,观察组FEV1、FVC、MVV高于对照组(P＜0.05);两组6MWT增加,Borg呼吸困难评分下降,观察组6MWT高于对照组,Borg呼吸困难评分低于对照组(P＜0.05);两组行为、情感、躯体、认知评分及总分均增加,观察组行为、情感、躯体、认知评分及总分高于对照组(P＜0.05).结论 艾迪注射液联合可穿戴设备肺康复训练显著提高晚期非小细胞肺癌化疗患者肺通气、运动功能,改善呼吸困难,缓解疲乏.

BackgroundThe 5-year event-free survival rate for childhood acute lymphoblastic leukemia (ALL) has increased to more than 85%. However, the 5-year overall survival rate in children with relapsed/refractory ALL did not exceed 50%. In the past decade, immunotherapies (such as blinatumomab and chimeric antigen receptor T-cell therapy) were approved for relapsed/refractory B-ALL, transforming the treatment environment for children with relapsed/refractory ALL.ObjectiveThis study aimed to explore how immunotherapy can be incorporated into salvage regimens for pediatric patients with relapsed/refractory ALL by retrospectively analyzing the diagnosis and treatment process of seven children with relapsed/refractory leukemia and observing the side effects of the two strategies and long-term survival.MethodsThe clinical features and treatment responses of patients aged <14 years with relapsed/refractory leukemia who received immunotherapy (including Chimeric Antigen Receptor T cell treatment and blinatumomab) at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between February 2014 and April 2022 were retrospectively analyzed.ResultsSeven children underwent immunotherapy. Five patients received immunotherapy and sequential allogeneic hematopoietic stem cell transplantation (HSCT), whereas the other two received only immunotherapy. Five patients achieved complete remission (71.4%). None of the patients had severe cytokine release syndrome. However, one developed grade 3 immune effector cell-associated neurotoxicity syndrome with prior leukoencephalopathy. The median follow-up period was 541 days (range, 186–3,180 days). No deaths were related to treatment. Three patients relapsed, two had CD19-negative recurrences, and the third showed CD19 antigen reduction. One patient died after disease progression, whereas the other died of HSCT-related complications. One patient abandoned the treatment after relapse and was lost to follow-up.ConclusionBlinatumomab and CAR T-cell therapy showed excellent remission rates and manageable toxicity in pediatric patients with relapsed/refractory leukemia. However, the duration of the remission was limited. Therefore, further prospective randomized clinical studies should be conducted to improve the long-term efficacy of immunotherapy.