Endobronchial involvement by diffuse large B-cell lymphoma (DLBCL) is rare in children, particularly in the setting of Epstein–Barr virus (EBV)-associated lymphoproliferation. We report an 8-year-old girl with a previous clinical diagnosis of chronic active Epstein–Barr virus infection and hemophagocytic lymphohistiocytosis who was readmitted with paronychia and fever. Imaging showed an obstructing mass in the right main bronchus with atelectasis, together with widespread lymphadenopathy and hepatic lesions. An initial ultrasound-guided fine-needle biopsy of a right cervical lymph node showed EBV-associated lymphoid hyperplasia without definite lymphoma. During the subsequent admission, a newly identified left submandibular mass was sampled by ultrasound-guided core-needle biopsy. However, no finalized pathological diagnosis was available when the airway obstruction progressed. Interventional bronchoscopy was therefore undertaken under general anesthesia to obtain bronchial tissue and improve airway patency. The mass was partially removed using electrosurgical snaring and cryo-extraction, followed by argon plasma coagulation for hemostasis. Preliminary assessment of the bronchial tissue and flow cytometry supported B-cell lymphoma, and systemic treatment was initiated on 5 June 2026. Final written pathology reports for both the submandibular and bronchial specimens, issued on 10 June, supported EBV-positive DLBCL with polymorphic morphology. Chest CT on 16 June showed improved aeration of the right lung and a patent right main bronchus. At the 16-day follow-up, the patient remained on treatment without recurrent dyspnea, hypoxemia, or a need for supplemental oxygen. In this patient, interventional bronchoscopy provided additional tissue while the lymph-node specimen was under evaluation and partially restored airway patency.

The clinical utility of measurable residual disease monitoring based on next-generation sequencing in T-cell acute lymphoblastic leukemia remains incompletely defined. Here we show the prognostic value of tracking clonal T-cell receptor gene rearrangements by next-generation sequencing in pediatric patients with T-cell acute lymphoblastic leukemia. Among the 101 patients with trackable clones, measurable residual disease levels at the end of consolidation strongly stratify 4-year event-free survival: 81.6% ± 5.6% for disease levels below 0.0001%, 61.9% ± 11.8% for 0.0001-0.1%, and 45.1% ± 12.1% for levels ≥ 0.1% (P = 0.004). Both T-cell receptor beta and gamma/delta rearrangements demonstrate prognostic significance. Notably, patients with multiparameter flow cytometry-negative but next-generation sequencing-positive measurable residual disease at the end of consolidation have significantly lower 4-year event-free survival compared to those achieving double-negative status (60.8% ± 9.4% vs. 84.9% ± 5.3%, P = 0.038). In conclusion, measurable residual disease monitoring by next-generation sequencing provides superior sensitivity and important clinical value, offering a potential strategy for precise risk stratification in T-cell acute lymphoblastic leukemia. The clinical value of next-generation sequencing for measurable residual disease (NGS-MRD) monitoring in T-cell acute lymphoblastic leukemia remains to be fully established. Tracking TCR rearrangements in pediatric patients, this study shows that NGS-MRD serves as a useful method to stratify outcomes and identifies high-risk cases.

BACKGROUND:Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressive and often fatal disorder. This study aimed to evaluate the stratification and treatment of pediatric Epstein-Barr virus-associated HLH (EBV-HLH) based on cytokine levels and clinical condition. METHODS:Pediatric patients newly diagnosed with EBV-HLH (n = 108) were risk stratified by cytokine and clinical criteria. Six were excluded for protocol violations. RESULTS:Among the 102 evaluable patients, 61 and 41 were classified as low and high risk and initially received dexamethasone treatment and HLH-94/04 regimens, respectively. Notably, 32.4% of children (33/102) were cured by dexamethasone monotherapy. The 12-month overall survival (OS) for the entire cohort was 86.3% (95% CI, 79.6%-93.0%), with 91.8% (95% CI, 84.9%-98.7%) and 78.0% (95% CI, 65.3%-90.7%) for patients at low and high risk, respectively (P = .037). Patients at low risk whose treatment shifted from dexamethasone to the HLH-94/04 regimen presented similar 12-month OS as those initially treated with the HLH-94/04 regimen (82.1% [95% CI, 68.0%-96.2%] vs 78.0% [95% CI, 65.3%-90.7%]; P = .589). In multivariate Cox regression model, risk group and response to initial treatment at 48-72 hours thereafter were associated with OS. CONCLUSIONS:A cytokine- and clinical-based risk stratification system, combined with dynamic response assessment, enables tailored treatment for pediatric patients with EBV-HLH.

Invasive fungal disease (IFD) remains a challenging complication and a leading cause of death in the treatment of childhood acute leukemia (AL). Blinatumomab is a novel bispecific antibody targeting CD19, with excellent anti-tumor effects against B cell malignancies, including B cell acute lymphoblastic leukemia (B-ALL). Compared with standard chemotherapy, blinatumomab causes less immunosuppression. This report describes two children with B-ALL who experienced recurrent high fever during induction chemotherapy. Next-generation sequencing (NGS) detected Aspergillus in bronchoalveolar lavage fluid, skin tissue, blood, and cerebrospinal fluid. After antifungal therapy, the patients received 9 courses of blinatumomab combined with reduced-dose chemotherapy. Symptoms, signs, and imaging findings improved significantly, B-ALL remained in continuous remission in both patients, and no cytokine release syndrome, neurotoxicity, or fungal infection recurrence occurred. These cases suggest that alternating blinatumomab with reduced-dose chemotherapy is both effective and safe for patients with B-ALL suffering life-threatening infections in the setting of ALL therapy.

NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P < 0.001 and P = 0.001, respectively). Multivariate Cox regression analyses demonstrated that patients harboring NUP98-r (P < 0.001) and WT1 mutations (P = 0.030) had worse relapse-free survival, and patients harboring NUP98-r (P < 0.008) presented lower overall survival. These investigations contribute to the understanding of the molecular characteristics, risk stratification, and prognostic evaluation of pediatric AML patients.

Severe sepsis and septic shock are life-threatening for pediatric hematology and oncology patient receiving chemotherapy. Th1/Th2 cytokines, C-reactive protein (CRP), and procalcitonin (PCT) are all thought to be associated with disease severity. The aim of this study was to prospectively verify the utility of Th1/Th2 cytokines and compare them with PCT and CRP in the prediction of adverse outcomes. Data on patients were collected from January 1, 2011, to December 31, 2020. Blood samples were taken for Th1/Th2 cytokine, CRP, and PCT measurements at the initial onset of infection. Severe infection (SI) was defined as severe sepsis or septic shock. Th1/Th2 cytokine levels were determined by using flow cytometric bead array technology. In total, 7,735 febrile episodes were included in this study. For SI prediction, the AUCs of IL-6, IL-10 and TNF-& alpha; were 0.814, 0.805 and 0.624, respectively, while IL-6 and IL-10 had high sensitivity and specificity. IL-6 > 220.85 pg/ml and IL-10 > 29.95 pg/ml had high odds ratio (OR) values of approximately 3.5 in the logistic regression. Within the subgroup analysis, for bloodstream infection (BSI) prediction, the AUCs of IL-10 and TNF-& alpha; were 0.757 and 0.694, respectively. For multiorgan dysfunction syndrome (MODS) prediction, the AUC of CRP was 0.606. The AUC of PCT for mortality prediction was 0.620. In conclusion, IL-6 and IL-10 provide good predictive value for the diagnosis of SI. For children with SI, IL-10 and TNF-& alpha; are associated with BSI, while CRP and PCT are associated with MODS and death, respectively.

Two hundred and thirty-one acute lymphoblastic leukemia (ALL) children with 1376 high-dose methotrexate (HD-MTX) courses (3-5 g/m2) were enrolled to analyze the influence of the plasma MTX concentration (CMTX) in ALL. The 24-h target peak CMTX (C24h) was set at 33 μmol/l for low-risk (LR) and 65 μmol/l for intermediate/high-risk (IR/HR) groups. The median C24h was 42.0 μmol/l and 69.7 μmol/l for LR and IR/HR groups, respectively. MTX excretion delay was observed in 14.6% of courses, which was more frequent in IR/HR groups (56.9% vs. LR group 40.2%, p = .014) and T-ALL patients (82.6% vs. B-ALL 47.1%, p = .001). MTX-related toxicities were more common in courses with MTX excretion delay. However, survival between the patients who failed to reach the target C24h or not, with or without MTX excretion delay, was comparable. These findings suggest that, owing to the effectiveness of risk stratification chemotherapy, CMTX does not exert an independent influence on the prognosis of childhood ALL.

INTRODUCTION:It is important to predict adverse outcomes in febrile children with hematology/oncology diseases. Procalcitonin (PCT) is a promising biomarker for the prediction of infection severity, but further studies have revealed its performance in excluding adverse outcomes of infection. IL-6 and IL-10 were reported to have a close association with those infection outcomes. The aim of the study was to investigate the performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal PCT.METHODS:This was a retrospective study conducted in a tertiary children's hospital in China over the past ten years. Inflammatory biomarkers, including IL-6, IL-10, PCT and C-reactive protein (CRP), were detected at the onset of infection. Separate analyses were conducted in patients with neutropenia and without neutropenia.RESULTS:In total, 5987 febrile cases were enrolled. For patients with neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with bloodstream infection (BSI), gram-negative bacteremia (GNB) and severe sepsis (SS), but only IL-6 and IL-10 were predictive of GNB and SS. For patients without neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with BSI, GNB and SS, but no biomarkers were predictive of adverse outcomes. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis in patients with neutropenia.CONCLUSIONS:IL-6 and IL-10 could be predictors for GNB and SS in febrile patients with neutropenia and had some association with unfavorable outcomes in febrile patients without neutropenia. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis.

OBJECTIVES:The purpose of this study was to explore the prognostic value of inflammatory biomarkers, including CRP, PCT, IL-6, IL-10,and the thrombotic biomarker D-dimer in predicting the development of severe infections and mortality in children with hematological malignancies. METHODS:A retrospective observational study was performed from October 2018 to December 2020 at the Children's Hospital, Zhejiang University School of Medicine.It collected clinical data of pediatric patients diagnosed with hematological malignancies who experienced febrile illnesses. Blood samples were obtained within 24 h of fever onset to test for D-dimer, Fibrinogen, PT, APTT, CRP, PCT and serum cytokine levels. RESULTS:Analysis revealed that with escalating infection severity, biomarkers such as CRP, PCT, IL-6, IL-10 and D-dimer progressively increased. The D-dimer level showed the highest accuracy (AUC of 0.930) in predicting mortality among children with severe infections. The combined analysis of IL-6 and D-dimer significantly improves the accuracy of prognosis in sepsis cases. A 60-day survival rate was lower for patients with D-dimer levels above 1.91 mg/L. CONCLUSION:In conclusion, D-dimer levels have proven to be a reliable biomarker for predicting mortality in children with hematological malignancies experiencing severe infections.

Purpose The 5-year survival rate of children with acute lymphoblastic leukemia (ALL) is 85–90%, with a 10–15% rate of treatment failure. Next-generation sequencing (NGS) identified recurrent mutated genes in ALL that might alter the diagnosis, classification, prognostic stratification, treatment, and response to ALL. Few studies on gene mutations in Chinese pediatric ALL have been identified. Thus, an in-depth understanding of the biological characteristics of these patients is essential. The present study aimed to characterize the spectrum and clinical features of recurrent driver gene mutations in a single-center cohort of Chinese pediatric ALL. Methods We enrolled 219 patients with pediatric ALL in our single center. Targeted sequencing based on NGS was used to detect gene mutations in patients. The correlation was analyzed between gene mutation and clinical features, including patient characteristics, cytogenetics, genetic subtypes, risk stratification and treatment outcomes using χ 2 -square test or Fisher’s exact test for categorical variables. Results A total of 381 gene mutations were identified in 66 different genes in 152/219 patients. PIK3R1 mutation was more common in infants ( P = 0.021). KRAS and FLT3 mutations were both more enriched in patients with hyperdiploidy (both P < 0.001). NRAS , PTPN11 , FLT3 , and KMT2D mutations were more common in patients who did not carry the fusion genes (all P < 0.050). PTEN mutation was significantly associated with high-risk ALL patients ( P = 0.011), while NOTCH1 mutation was common in middle-risk ALL patients ( P = 0.039). Patients with ETV6 or PHF6 mutations were less sensitive to steroid treatment ( P = 0.033, P = 0.048, respectively). Conclusion This study depicted the specific genomic landscape of Chinese pediatric ALL and revealed the relevance between mutational spectrum and clinical features of Chinese pediatric ALL, which highlights the need for molecular classification, risk stratification, and prognosis evaluation.

目的:探讨心理干预在孤独症患儿家长中的应用效果.方法:选取2022年1～6月广西壮族自治区妇幼保健院儿童康复科收治的孤独症患儿家长作为研究对象,随机分为对照组和干预组,每组各40例,对照组予常规健康教育,干预组在此基础上实施心理干预.比较两组自我效能感量表(GSES)及抑郁(SDS)、焦虑(SAS)自评量表评分,比较两组遵医总依从率.结果:干预组孤独症患儿家长GSES量表评分、遵医总依从率显著高于对照组,差异有统计学意义(P<0.05);干预组SAS、SDS量表评分低于对照组,差异有统计学意义(P<0.05).结论:心理干预能够提高孤独症患儿家长自我效能、遵医依从性,缓解孤独症患儿家长抑郁、焦虑情绪.

While the prognostic role of immunoglobulin heavy chain locus (IGH) rearrangement in minimal residual disease (MRD) in pediatric B-acute lymphoblastic leukemia (B-ALL) has been reported, the contribution of light chain loci (IGK/IGL) remains elusive. This study is to evaluate the prognosis of IGH and IGK/IGL rearrangement-based MRD detected by next-generation sequencing in B-ALL at the end of induction (EOI) and end of consolidation (EOC). IGK/IGL rearrangements identify 5.5% of patients without trackable IGH clones. Concordance rates for IGH and IGK/IGL are 79.9% (cutoff 0.01%) at EOI and 81.0% (cutoff 0.0001%) at EOC, respectively. Patients with NGS-MRD < 0.01% at EOI or <0.0001% at EOC present excellent outcome, with 3-year event-free survival rates higher than 95%. IGH-MRD is prognostic at EOI/EOC, while IGK-MRD at EOI/EOC and IGL-MRD at EOI are not. At EOI, NGS identifies 26.2% of higher risk patients whose MRD < 0.01% by flow cytometry. However, analyzing IGK/IGL along with IGH fails to identify additional higher risk patients both at EOI and at EOC. In conclusion, IGH is crucial for MRD monitoring while IGK and IGL have relatively limited value.

The aim of this study is to investigate the clinical potential of immune microenvironment in peripheral blood for the severity and therapeutic efficacy of Langerhans cell histiocytosis (LCH). A total of 200 newly diagnosed children with LCH during 10 years was enrolled for analysis in this study. Peripheral blood samples were acquired from patients before treatment in our hospital and immune indicators were detected by a four-color flow cytometer. The levels of CD3 + CD8 + T cell, CD3 + CD4 + HLA-DR + T cell, CD3 + CD8 + HLA-DR + T cell, IL-4, IL-6, IL-10 and IFN-γ in peripheral blood were markedly elevated in LCH patients vs. healthy controls. Patients with multiple system with risk organ involvement (MS-RO + ) exhibited higher levels in IL-6, IL-10 and IFN-γ, CD3 + CD4 + HLA-DR + T cell and CD3 + CD8 + HLA-DR + T cell, compared to those in patients without risk organ involvement (RO-). Patients who responded effectively to initial chemotherapy showed significantly lower levels of IL-4, IL-10, IFN-γ, CD3 + CD4 + HLA-DR + T cell and CD3 + CD8 + HLA-DR + T cell in peripheral blood, compared to those in patients who did not respond to initial chemotherapy. Furthermore, univariate analyses were performed that the higher levels of CD3 + CD4 + HLA-DR + T cells, CD3 + CD8 + HLA-DR + T cells and IL-10 in peripheral blood were related to non-response in LCH after initial chemotherapy. Immune microenvironment in peripheral blood may be associated with the severity and treatment response of LCH. The levels of CD3 + CD4 + HLA-DR + T cells, CD3 + CD8 + HLA-DR + T cells and IL-10 may be biomarkers to predict treatment response of LCH patients.

CAR-T therapies to treat T-cell malignancies face unique hurdles. Normal and malignant T cells usually express the same target for CAR, leading to fratricide. CAR-T cells targeting CD7, which is expressed in various malignant T cells, have limited expansion due to fratricide. Using CRISPR/Cas9 to knockout CD7 can reduce the fratricide. Here we developed a 2-in-1 strategy to insert EF1α-driven CD7-specific CAR at the disrupted CD7 locus and compared it to two other known strategies: one was random integration of CAR by a retrovirus and the other was site-specific integration at T-cell receptor alpha constant (TRAC) locus, both in the context of CD7 disruption. All three types of CD7 CAR-T cells with reduced fratricide could expand well and displayed potent cytotoxicity to both CD7+ tumor cell lines and patient-derived primary tumors. Moreover, EF1α-driven CAR expressed at the CD7 locus enhances tumor rejection in a mouse xenograft model of T-cell acute lymphoblastic leukemia (T-ALL), suggesting great clinical application potential. Additionally, this 2-in-1 strategy was adopted to generate CD7-specific CAR-NK cells as NK also expresses CD7, which would prevent contamination from malignant cells. Thus, our synchronized antigen-knockout CAR-knockin strategy could reduce the fratricide and enhance anti-tumor activity, advancing clinical CAR-T treatment of T-cell malignancies.

The robust and stable expression of CD38 in T-cell acute lymphoblastic leukemia (T-ALL) blasts makes CD38 chimeric antigen receptor (CAR)-T/natural killer (NK) a potential therapy for T-ALL. However, CD38 expression in normal T/NK cells causes fratricide of CD38 CAR-T/NK cells. Here a "2-in-1" gene editing strategy is developed to generate fratricide-resistant locus-specific CAR-T/NK cells. CD38-specific CAR is integrated into the disrupted CD38 locus by CRISPR/Cas9, and CAR is placed under the control of either endogenous CD38 promoter (CD38KO/KI ) or exogenous EF1α promoter (CD38KO/KI EF1α). CD38 knockout reduces fratricide and allows the expansion of CAR-T cells. Meanwhile, CD38KO/KI EF1α results in higher CAR expression than CD38KO/KI in both CAR-T and CAR-NK cells. In a mouse T-ALL model, CD38KO/KI EF1α CAR-T cells eradicate tumors better than CD38KO/KI CAR-T cells. Surprisingly, CD38KO/KI CAR-NK cells show superior tumor control than CD38KO/KI EF1α CAR-NK cells. Further investigation reveals that endogenous regulatory elements in NK cells lead to higher expression of CD38 CAR than in T cells, and the expression levels of CAR affect the therapeutic outcome of CAR-T and CAR-NK cells differently. Therefore, these results support the efficacy of CD38 CAR-T/NK against T-ALL and demonstrate that the "2-in-1" strategy can resolve fratricide and enhance tumor eradication, paving the way for clinical translation.

目的 探讨家庭康复护理在自闭症患儿社会交往障碍治疗中的应用价值.方法 选择2021年3-9月本院收治的自闭症患儿80例作为研究对象,将患儿住院号纳入计算机展开随机分组,即对照组与观察组,各40例.对照组采用常规护理,观察组采用家庭康复护理.对比两组干预前、干预3个月后孤独症行为评定量表(ABC),儿童孤独症评定量表(CARS)评分,Gesell发育量表中各维度发育商及干预3个月后护理满意度.结果 干预前,两组ABC、CARS评分比较,组间差异无统计学意义(P＞0.05);干预3个月后,观察组ABC、CARS评分均低于对照组,组间差异有统计学意义(P＜0.05).干预前,两组Gesell发育量表各维度发育商比较,组间差异无统计学意义(P＞0.05);干预3个月后,观察组Gesell发育量表中适应性行为、语言行为和个人-社交行为发育商均明显高于对照组,组间差异有统计学意义(P＜0.05).干预3个月后,观察组护理满意度明显高于对照组,差异有统计学意义(P＜0.05).结论 自闭症患儿社会交往障碍治疗期间采取家庭康复护理干预模式,能使患儿语言发育、社会交往能力显著提升,生活质量明显改善,护理满意度较高.

目的 探讨医院-社区联动管理模式在地中海贫血(地贫)育龄妇女优生优育管理中的应用效果.方法 回顾性分析2018年1月至2021年12月与广西壮族自治区妇幼保健院有合作关系的3个社区卫生服务中心所管理的地贫育龄妇女的临床资料.按医院-社区联动管理模式实施时间将地贫育龄妇女分为对照组(2018年1月至2019年12月,35例)和观察组(2020年1月至2021年12月,38例).对照组接受常规健康教育,观察组在常规健康教育的基础上采用医院-社区联动管理模式进行优生优育管理.比较两组地贫妇女孕早期、入院待产时的血红蛋白水平、贫血程度及妊娠结局.结果 孕早期两组地贫孕妇的血红蛋白水平和贫血程度差异均无统计学意义(均P>0.05);入院待产时观察组地贫孕妇的血红蛋白水平高于对照组、贫血程度轻于对照组(均P<0.05).观察组的剖宫产率和低出生体重儿发生率均低于对照组(均P<0.05),但两组早产发生率差异无统计学意义(P>0.05).结论 医院-社区联动管理模式有助于改善地贫孕妇孕晚期的贫血状况,降低剖宫产率和低出生体重儿发生率.该模式可实现医院与社区间的双向管理,有利于提升对地贫育龄妇女优生优育的管理效果.

近年来儿童急性T淋巴细胞性白血病的长期生存率已明显提高,尤其是欧美发达国家,5年总生存率接近90％,但我国目前报道的长期生存率较国际领先水平尚有一定差距.急性T淋巴细胞性白血病易出现诱导失败且复发率较高,而复发/难治性急性T淋巴细胞性白血病的治疗又极其棘手,有效的治疗药物非常有限,预后极差,长期生存率不到25％,极大影响急性T淋巴细胞性白血病的治疗效果.为了提高对复发/难治性急性T淋巴细胞性白血病的诊治水平,本文对其复发的危险因素、复发和耐药机制以及治疗进展进行综述.