Abstract Background: Relapse remains a major challenge in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL). This study aims to identify the specific genomic and cellular markers that drive treatment failure and are associated with relapse and poor Event-Free Survival (EFS) in Chinese pediatric B-ALL patients. Methods: We performed an integrated multi-omic analysis on a cohort of 105 Chinese pediatric B-ALL patients, including 13 EFS Event (relapse plus died) cases. The cohort was profiled using ultra-deep gene panel sequencing (N=87), single-cell RNA-sequencing (scRNA-seq, N=52), and VDJ-sequencing (N=40). We integrated genomic, transcriptomic, and immune repertoire data to identify biomarkers associated with relapse and EFS. Associations were tested using Fisher's Exact Test, the Wilcoxon rank-sum test, and Cox regression. Results: Our scRNA-seq and VDJ-seq analyses revealed the cellular landscape of relapse. We found a positive correlation between B-ALL blast proportion and BCR clonality and a negative correlation between T-cell proportion and TCR clonality (p=0.041). Notably, relapsed patients showed a higher BCR clonality but a highly polyclonal TCR repertoire, suggesting immune failure. We identified that mutations in a curated panel of ALL-Drivers was significantly associated with relapse status (p=0.033) and a higher B-ALL blast percentage (p=0.013). And the higher ALL-Drivers VAF burden phenotype correlates with relapse status (p=0.006). The non-relapse patients were found exhibited an “immune-hot" phenotype, characterized by significantly higher T-cell exhaustion and cytotoxicity scores (p<0.001). This state of active immune engagement is associated with PD-1/PD-L1 pathway. Relapse was associated with an "immune-cold" state, lacking this active T-cell engagement. Finally, survival analysis and KM plot confirmed the prognostic significance of these findings. The presence of an ALL-Driver is significantly associated with poor Event-Free Survival (p=0.021). Conclusion: Our findings reveal a biological pathway to poor prognosis. ALL-Drivers are linked to a high B-ALL blasts burden. This high-risk state is strongly correlated with patient relapse and is characterized by an "immune-cold" microenvironment, defined by the absence of the PD-L1 mediated T-cell exhaustion and cytotoxicity signature seen in non-relapsed patients. Citation Format: Dan Yu, Yanni Hu, Xue Tang, Junlin Wang, Junwen Wang, Jianwen Xiao. Genomic drivers and an immune-cold microenvironment are associated with relapse in Chinese pediatric B-ALL [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2723.

Background This study evaluated the efficacy and safety of dabrafenib or trametinib in pediatric Langerhans cell histiocytosis (LCH) patients with skeletal involvement, for whom conventional therapies offer limited benefit. Methods A single-center retrospective analysis was conducted on 30 children with pathologically confirmed, bone-involved LCH who received dabrafenib or trametinib due to severe, refractory, or chemotherapy-intolerant disease. Primary endpoints were imaging-based objective response rate (ORR) and disease control rate (DCR). Progression-free survival (PFS) was defined as time from targeted therapy initiation to disease progression (AD-Mixed/AD-Worse) or last follow-up, with AD-Better/AD-Stable considered disease control, including subgroup analysis by BRAF mutation status (V600E vs non-V600E). Results The median age at diagnosis was 3.1 years with a male-to-female ratio of 2:1. The BRAF V600E mutation was detected in 27 patients (90.0%), with two patients harboring BRAF non-V600E mutations and one patient carrying a MAP2K1 mutation. The median duration of targeted therapy was 17.7 months. At last follow-up, 23.3% (7/30) achieved active disease-better status, and 60.0% (18/30) had active disease-stable status, resulting in an ORR of 23.3% and a DCR of 83.3%. All patients survived. Notably, patients with non-V600E driver mutations (BRAF class II or MAP2K1, cases 22, 26, 28) received MEK inhibitor therapy (trametinib) and derived clinical benefit, highlighting the importance of precise genomic characterization. Drug-related adverse events occurred in 20.0% (6/30) of patients, consisting of mild cutaneous toxicities (e.g., rash, paronychia). Conclusions In pediatric LCH with bone involvement, particularly in refractory or chemotherapy-intolerant cases, short- to intermediate-term targeted therapy with dabrafenib or trametinib achieved a high disease control rate (83.3%) with a favorable safety profile. Notably, patients with non-V600E driver mutations (BRAF class II or MAP2K1) derived clinical benefit from MEK inhibition, underscoring the importance of comprehensive genomic testing. These real-world findings support the use of targeted therapy in this challenging population.

Chromosomal translocations involving nucleoporin (NUP) loci, such as NUP98 and NUP214, are recurrent in acute myeloid leukemia (AML). However, the intrinsic functions of wild-type nucleoporins in AML remain largely unknown. By screening the NUP family, we identified NUP214 as a frequently overexpressed gene and a critical fitness determinant in leukemia stem cells (LSCs). NUP214 acts as a conserved driver of LSC survival by restricting heme catabolism, limiting Fe²⁺ accumulation, and suppressing lipid peroxidation. Conversely, NUP214 deficiency leads to upregulation of heme oxygenase 1 (HMOX1) and arachidonate 15-lipoxygenase (ALOX15), causing heme exhaustion and excessive lipid peroxidation, which ultimately triggers ferroptosis in LSCs and impairs AML progression. Mechanistically, NUP214 translocates into the nucleoplasm where it blocks Sub1-mediated RNA polymerase II recruitment to repress transcription of the key pro-ferroptotic genes HMOX1 and ALOX15, revealing a non-canonical role beyond its nuclear pore function. Furthermore, we developed the small-molecule compound 0449-b, which acts as a selective NUP214 degrader by recruiting NUP214 to the Cullin5-Rbx2 E3 ligase complex, inducing its neddylation and proteasomal degradation. 0449-b potently triggers LSC ferroptosis and exhibits anti-leukemic activity in vivo, while sparing normal hematopoietic stem cells. Collectively, our findings establish NUP214 as a critical oncoprotein that orchestrates heme metabolism and lipid peroxidation to sustain LSCs, and highlight NUP214-targeted degradation as a promising intervention strategy for AML.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a fatal hyperinflammatory disorder distinct from self-limiting EBV-induced infectious mononucleosis (IM). However, the immunological mechanisms underlying the divergence between benign EBV infection and fulminant HLH-particularly in the absence of inherited immunodeficiency-remains unclear, and systematic comparisons of immune landscapes across EBV-associated disease spectra are lacking. In this study, by enrolling children with IM and healthy volunteers as controls, we utilize single-cell RNA sequencing to identify unique immunological characteristics of EBV-HLH. Our analysis indicates that patients with EBV-HLH exhibite widespread activation of NF-κB signaling pathway. Furthermore, excessive cytokine secretion by T and NK cells is observed, along with a shift in monocyte differentiation towards an inflammatory phenotype, and the aggregation of IDO1+ monocytes. Metabolic pathway analysis reveals that L-kynurenine, a downstream metabolite of IDO1, is specifically elevated in EBV-HLH and mediates the production of multiple pro-inflammatory cytokines. Collectively, our study maps the immune landscape in pediatric EBV-HLH at single-cell resolution, uncovering potential role of IDO1+ monocytes and L-kynurenine as biomarkers.

Current risk subgroups for acute myeloid leukemia (AML) rely primarily on molecular and cytogenetic markers. These subgroups have distinct clinicopathological and molecular characteristics and are the basis for classifying disease subgroups currently undergoing clinical trials and initial subgroup-oriented therapies. However, substantial biological heterogeneity and differences in survival are apparent within each subgroup, so transcriptome-based molecular subgroup identification and prognostic stratification in pediatric acute myeloid leukemia remain to be resolved. In this study, we conducted a comprehensive analysis of transcriptomic data for AML using data from public datasets and constructed a new prognostic prediction model. We first downloaded the transcriptome data of the GDC Data Portal and the gene set of MsigDB for survival and cluster analysis and reclassified AML into 8 different molecular subgroups. The expression profiles, changes in the immune microenvironment, biological functions and pathways, and clinical features among these subpopulations were further studied. The classification prediction model is then developed using four machine learning algorithms: RF, SVM, XGBoost, and DT. The XGBoost method showed the best performance. The vital feature variables in XGBoost suggest that HSD17B10, NDUFS8, ASCL5, FADS2, and COX8A were critical factors in identifying the prognosis of AML. We only found that NDUFS8 and FADS2 had been reported in AML, and the remaining three gene new prognostic markers for AML have not been reported before, but they have all been reported to be associated with cancer. we identified eight transcriptome-based molecular subgroups of AML and further assessed differences in the molecular landscape, immune networks, and signaling pathways underlying these subpopulations. Additionally, the prognostic models comprising 62 genes was proposed and demonstrated to have remarkable predictive value. Overall, we identified a new molecular subpopulation of AML, which improved disease risk stratification and established a prognostic model for AML, which demonstrated favorable performance in retrospective validation. Since this study relies on retrospective data, further prospective analysis is required to confirm its ability to accurately reflect patient prognosis.

This study aimed to develop and validate a risk prediction model for moderate to severe bleeding in children with immune thrombocytopenia (ITP). Data from 286 ITP patients were prospectively collected and randomly split into training (80

Introduction: Acute lymphoblastic leukemia (ALL) is one of the most common malignant tumors in children and a leading cause of mortality in children and adolescents. The chimeric antigen receptor (CAR-T) cell therapy has revolutionized the treatment of relapsed/refractory (R/R) B-cell ALL, with the first FDA-approved product, Kymriah (tisagenlecleucel) developed by Novartis, significantly improving remission rates and survival times. pCAR-19B is an autologous CAR-T cell product with an optimized humanized CD19-specific single-chain variable fragment (scFv) designed to address safety concerns. pCAR-19B has been granted “Breakthrough Therapy Designation” by the China National Medical Products Administration for treating B-ALL. This report presents the efficacy and safety outcomes of pCAR-19B in a pivotal clinical trial involving Chinese pediatric and young adult patients with R/R B-cell ALL. Methods: This phase 2 trial (NCT05334823) was a single-arm, open-label, multicenter study. Patients aged ≥ 3 and ≤ 21 years at screening with confirmed CD19+ R/R B-ALL were included. The primary endpoint was the overall remission rate (ORR), defined as complete remission (CR) plus CR with incomplete blood recovery (CRi) within 3 months post-infusion. Results: As of April 18th, 2024, 89 patients had been enrolled and underwent leukapheresis, with 64 patients receiving pCAR-19B infusion. There were no cases of manufacturing failure. Among the infused patients, 6.25%(4/64）were refractory and 93.75%(60/64) had relapsed to multiple lines of prior therapy or allogeneic stem cell transplant. The median age was 11 years (range 3-21), and 56.25% (36/64) were male. Additionally, 75% (48/64) of the patients carried at least one high-risk gene. The median bone marrow (BM) blast burden at baseline was 58.3% (range 5%-98%) with a heavy BM blast burden (≥50%) observed in 56.25% of the patients. At a median follow-up of 211 days (range 35-750), the best ORR was 90.63% (58/64), with 78.13% of patients (50/64) achieving CR and 12.5% of patients (8/64) achieving CRi, surpassing the efficacy of the commercial anti-CD19 CAR-T therapy products reported in R/R B-ALL. 98.27% (57/58) of patients with ORR achieved negative minimal residual disease (MRD)-negative remission. The ORR at 3 months was 76.56% (49/64). The median duration of response (DOR) was 10.61 months (95% confidence interval 7.66-20.96). The median overall survival (OS) was 23.92 months (95% confidence interval 9.86-NR). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 98.44% and 50% of patients, respectively. Grade ≥3 CRS and ICANS were observed in 29.69% and 39.06% of patients, respectively. The median duration of Grade ≥3 CRS and ICANS was 4 days and 3 days, respectively. There were no deaths attributed to CRS or ICANS. Conclusions: Despite a heavy burden of BM blasts and a high risk of genetic variations, pCAR-19B demonstrated high remission rates, achieved a high rate of MRD-negative remission, durable responses, and a tolerable safety profile. This study represents the first pivotal clinical trial of childhood B-ALL in an Asian population, offering a new treatment option for Chinese pediatric and young adult patients with R/R B-ALL.

BackgroundVoriconazole (VRZ) is involved in a variety of drug‒drug interactions (DDIs), but few studies have reported adverse events (AEs) associated with the DDIs of VRZ. The primary goal of this study was to analyse the potential risk factors for AEs caused by DDIs between VRZ and other drugs via the OpenVigil FDA platform and to provide a reference for preventing VRZ DDIs and monitoring clinically related adverse drug events.MethodsA retrospective pharmacovigilance study was conducted to investigate the AEs related to DDIs between VRZ and four categories of drugs: proton pump inhibitors (PPIs), non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressants, and other antibacterial drugs. AE information for the target drugs from the first quarter of 2004 to the third quarter of 2022 was downloaded from the OpenVigil FDA data platform. Four frequency statistical models—the reporting ratio method, Ω shrinkage measure model, combination risk ratio model, and the chi-square statistics model—were used to analyse the AEs related to DDIs and evaluate the correlation and influence of sex and age between the drug(s) and the target AEs detected.ResultsA total of 38 drugs were included, with 262 AEs detected by at least one of the four models and 48 AEs detected by all four models. Some 77 detected AEs were significantly positively correlated with DDIs and were related to higher reporting rates of AEs than when used alone. Graft-versus-host disease was the AE that had the strongest correlation with the drug interaction between VRZ and immunosuppressants (tacrolimus, mycophenolate mofetil, cyclophosphamide, and cyclosporine), and multiple organ dysfunction syndrome was correlated with VRZ in combination with other antibacterial drugs (linezolid, meropenem, cefepime, and vancomycin). Significant sex and age differences in the target AEs were detected for five and nine target drugs, respectively. For VRZ in combination with linezolid, aggravated conditions and respiratory failure should be given more attention in male patients, and mycophenolate mofetil and respiratory failure in female patients. When conditions are aggravated, febrile neutropenia and septic shock should be of particular concern in patients over 18 years of age who use VRZ in combination with ceftazidime, ciprofloxacin, or cytarabine. In patients aged under 18, septic shock should be considered when VRZ is used in combination with meropenem and dexamethasone.ConclusionAEs related to DDIs should receive more attention when VRZ is used in combination with PPIs (renal impairment), NSAIDs (constipation and renal failure), immunosuppressants (graft versus host disease, septic shock) and other antibacterial drugs (multiple organ dysfunction syndrome, febrile neutropenia, and respiratory failure). Considering the influence of sex and age differences in VRZ DDIs, these factors need to be considered when assessing the risk of AEs in patients receiving VRZ and other drugs.

Blinatumomab has shown to improve survival outcomes in B-cell acute lymphoblastic leukemia (B-ALL) patients with measurable residual disease (MRD) detected by multiparametric flow cytometry (MFC). However, data on blinatumomab clearing MRD with high sensitivity remain scarce. This study evaluates the effectiveness of blinatumomab in eradicating low levels of MRD, as detected by droplet digital PCR (ddPCR) but undetectable by MFC, in children with B-ALL. Patients (n = 9) whose MRD was undetectable by MFC but detectable by ddPCR after chemotherapy and followed by blinatumomab consolidation were included retrospectively. After the administration of blinatumomab, 5 out of 9 patients (55.56

Background:Exploring sensitive prognostic methods for patients with relapsed or refractory neuroblastoma (NB) is critical. The five NB genes (NB5) share a common trait: they are highly expressed in NB. Previous studies have identified their expression levels as markers for guiding micrometastasis. This study aimed to explore whether an improved NB5 detection method is superior to flow cytometry for predicting NB metastasis, measurable residual disease (MRD), and prognosis, and whether this result could serve as an independent factor to influence progression-free survival (PFS).Methods:We utilized reverse transcriptase polymerase chain reaction (RT-PCR) to assess the expression of NB5 (CHGA, DCX, DDC, PHOX2B, and TH) in bone marrow (BM), peripheral blood (PB), or cerebrospinal fluid (CSF) samples collected from 71 patients. The correlation between gene expression changes and clinical characteristics, as well as survival rates, based on 113 detections were analyzed. The NB5 detection results' sensitivity and specificity in all 71 patients collected from six research centers with a median follow-up of 14 months were assessed.Results:PB specimens showed 100% concordance with the BM specimens in terms of positive results. Furthermore, the BM specimens exhibited an additional 45.455% (5/11) positive results compared to the 34.091% (30/88) of PB specimens. The BM specimens were positive for NB5 assay, which was significantly higher than the positive results of flow cytometric MRD (15/88, 17.045%). NB5 was mainly expressed in newly diagnosed patients (P=0.043) and positive patients with flow cytometric MRD (P<0.001) or BM morphology (P<0.001). Positive rates of droplet digital PCR (ddPCR) were consistent with those of quantitative RT-PCR (qRT-PCR) in BM (13/18, 72.222%). However, in PB, the positive rate of ddPCR (2/5, 40.000%) was higher than that of qRT-PCR. A total of 38 specimens (BM, PB, CSF) were detected as positive under qRT-PCR. Among the positive results, the analysis revealed a significant difference between the CHGA and TH in pairwise comparisons (P=0.005). PFS analysis showed that among MRD-negative patients, the survival time of the NB5-positive group was significantly lower than that of NB5-negative group (27.408±10.791 vs. 35.961±3.084 months; P=0.034), and in the Cox regression model, risk stratification based on NB5 expression level was an independent prognostic factor for relapsed or refractory disease [95% confidence interval (CI):1.020 to 9.099, hazard ratio (HR) =3.046, P=0.046]. Combining the follow-up results, we found that the sensitivity and specificity of NB5 detection were both 100%.Conclusions:In our study, the improved NB5 detection method showed significantly higher sensitivity in assessing tumor relapse or residual disease compared to flow cytometric MRD. Moreover, it provided a more accurate assessment of treatment efficacy and prognosis. These findings support NB5 detection as an effective method for further stratification and monitoring of patients with relapsed or refractory NB.

Objective To investigate the genomic signatures and prognosis of advanced-stage T cell lymphoblastic lymphoma (T-LBL) and to examine the relationship between T-LBL and T cell acute lymphoblastic leukemia (T-ALL). Methods 35 Chinese T-LBL children with stage III or IV disease were recruited for this study. They were treated with combination chemotherapy and whole exome sequencing. The relationship of the clinical features, prognosis and specific gene mutations was researched. Gene chips of T-LBL and T-ALL were downloaded from a database, and differential gene expression was analyzed. Results Germline causal gene mutations (CARS or MAP2K2) were detected in 2 patients; 3.06 ± 2.21 somatic causal gene mutations were identified in the 35 patients, and somatic mutations were observed in the NOTCH1, FBXW7, PHF6 and JAK3 genes. NOTCH1 mutations were significantly associated with FBXW7 mutations, and the age at diagnosis of patients with NOTCH1-FBXW7 mutations was less than that of patients without such mutations ( P < 0.05). 32 patients achieved complete remission (CR), and 14 and 18 patients were classified into the intermediate risk (IR) group and high risk (HR) group. During a median follow-up of 44 months, 3 patients relapsed. Three-year prospective event free survival (pEFS) was 82.286%, and no significant differences of pEFS were found for different sexes, ages, or statuses of NOTCH1-FBXW7 mutations, ( P > 0.05); however, the mean survival time of the IR group was longer than that of the HR group ( P < 0.05). Differential expression of genes in the T-LBL and/or T-ALL datasets was analyzed using the R package limma, and 1/3 of the differentially expressed genes were found in both the T-ALL and T-LBL datasets. High expression of PI3K-Akt signal pathway genes and the USP34 gene was found in the T-LBL dataset. Conclusion Although T-ALL and T-LBL both originate from precursor T-cells and are considered different manifestations of the same disease and the outcome of T-LBL is favorable when using T-ALL-based chemotherapy, there are differences in the gene distribution between T-LBL and T-ALL. It seems that the PI3K-Akt signaling pathway and the USP34 gene play important roles in T-LBL, but medicines targeting the USP34 gene or the PI3K-Akt pathway may be invalid.

Primary lymphoma of the bone (PLB) is a rare form of extranodal lymphoma. The clinical features and imaging findings of PLB are not specific. Histological examination and immunophenotyping is the gold standard for diagnosis. We reported three cases, all diagnosed with B-cell lymphoblastic lymphoma. The first patient is a 4-year-old boy with 6 months history of PLB. Lytic permeative areas with soft-tissue masses showed on imaging. A mutation of the FANCA gene of this patient was detected through whole exome sequencing (WES). The second patient is a 17-year-old boy with multiple areas of pain over 2 months. Flurodeoxyglucose positron emission tomography/computed tomography showed that the density of multiple bones was slightly increased. WES revealed a heterozygous splice site variation in the SBDS gene. The third patient is a 3-year-old boy with swelling and pain of the left knee joint and fever for 43 days. An oval like lesion area appeared on imaging. The display of case details helps to diagnose and understand PLB. The correlation between the occurrence and progression of the disease and FANCA gene and SBDS gene mutations remains to be studied.

病例资料 病例1:女,4岁7个月时因"贫血1年余,加重1个月"第1次住院.除贫血外,伴生长发育迟缓、反复上呼吸道感染,有茶色尿.无咳嗽、呕吐、腹痛、腹泻,无骨关节疼痛及浮肿,无皮肤黏膜出血、黑便、血尿.院外血常规检测提示血红蛋白波动在54～101g/L,骨髓细胞学提示增生性贫血,无输血史.系G5P3,不挑食.父母近亲婚配,同胞中G1P1,4岁时因贫血去世(具体原因不详),G2P2及G6P4均体健,G7P5为病例2,G3及G4均系孕8周前人工流产(因无生育计划),否认遗传性疾病及血液肿瘤病史.

Background The real-world experiences of Hemophilia A (HA) patients receiving emicizumab prophylaxis in China are insufficient due to the high cost and later approval of emicizumab. In this study, we retrospectively analyzed Chinese HA patients with or without factor VIII (FVIII) inhibitors receiving emicizumab prophylaxis with the aim to investigate the efficacy and safety of emicizumab as well as the current status and effect of different doses of emicizumab in a real-world setting. Methods HA patients with or without FVIII inhibitors receiving emicizumab prophylaxis between June 2019 and June 2023 in China were included in the study. Data of HA patients including children and adults were retrospectively gathered from 27 hospitals all over the country. For each patient, the anonymized data were collected and telephone follow-ups were conducted to make sure the intact information collected as much as possible. Low dose and higher dose of emicizumab were defined as monthly dose <3 mg/kg and monthly dose ≥3 mg/kg, respectively. All analyses were performed using SPSS software version 25.0 (IBM Corporation, Armonk, New York, USA). Intraindividual comparisons were performed by nonparametric paired tests. Results A total of 127 male patients (10.2% [n=13] ≥18 years old; 89.8% [n=114] <18 years old) were enrolled in our study (severe: moderate = 103:24). Of these, 42 (33.1%) had FVIII inhibitors at initiating emicizumab. The median (interquartile range [IQR]) duration of emicizumab treatment was 16.0 (9.0-30.0) months. The median (IQR) annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR) after emicizumab were 0.5 (0-1.5) and 0 (0-0), respectively (calculated in patients treated with emicizumab >6 months). Among the 127 patients, 67 (52.8%) patients had no bleeds at all. No intracranial hemorrhage occurred after emicizumab. Adverse events were reported in 12 (9.4%) patients and 10 (83.3%) were injection-site reactions. There were no deaths, thromboembolic events, or thrombotic microangiopathies in our study. Two (8.0%) patients had treated epistaxis after emicizumab with low dose compared with 0 (0.0%) with higher dose ( P =0.037). Four (16.0%) patients had target joints after emicizumab with low dose compared with 1 (1.0%) with higher dose ( P =0.005) (Table 1). There were no significant differences between low dose and higher dose of emicizumab prophylaxis in ABR, AJBR, the proportion of zero bleeds, the proportion of adverse events, and so on. The median (IQR) ABR was 5.0 (2.0-14.0) with prior treatment compared with 0.5 (0-1.5) with emicizumab, an 90% reduction in ABR with P value <0.001 (Table 2).Also, the use of emicizumab was also associated with significant reduction in AJBR ( P <0.001), number of target joints ( P <0.001), number of intracerebral hemorrhages ( P <0.001), inhibitor titer ( P =0.016), and days away from school/work ( P <0.001). Conclusion In this multi-center study, we indicated the efficacy and safety of emicizumab and that low dose and higher dose of emicizumab had similar efficacy in Chinese HA patients without increasing adverse events.

Objectives: There have been limited studies concerning the safety and efficacy of linezolid (LZD) in children. This study aimed to evaluate the association between LZD exposure and clinical safety and efficacy in Chinese pediatric patients.Methods: This retrospective cross-sectional study included patients ≤18 years of age who received ≥3 days of LZD treatment between 31 January 2015, and 31 December 2020. Demographic characteristics, medication information, laboratory test information, and bacterial culture results were collected from the Hospital Information System (HIS). Exposure was defined as AUC24 and calculated by the non-linear mixed-effects modeling program (NONMEM), version 7.2, based on two validated population pharmacokinetic models. Binary logistic regression analyses were performed to analyze the associations between AUC24 and laboratory adverse events, and receiver operating characteristic curves were used to calculate the cut-off values. Efficacy was evaluated by bacterial clearance.Results: A total of 413 paediatric patients were included, with an LZD median (interquartile range) dose, duration, clearance and AUC24 of 30.0 (28.1-31.6) mg/kg/day, 8 (4‒15) days,1.31 (1.29-1.32) L/h and 81.1 (60.6-108.7) mg/L·h, respectively. Adverse events associated with TBil, AST, ALT, PLT, hemoglobin, WBC, and neutrophil count increased during and after LZD treatment when compared with before medication (p < 0.05), and the most common adverse events were thrombocytopaenia (71/399, 17.8%) and low hemoglobin (61/401, 15.2%) during the LZD treatment. Patients with AUC24 higher than 120.69 mg/L h might be associated with low hemoglobin 1–7 days after the end of the LZD treatment, and those with an AUC24 higher than 92.88 mg/L∙h might be associated with thrombocytopaenia 8–15 days after the end of the LZD treatment. A total of 136 patients underwent bacterial culture both before and after LZD treatment, and the infection was cleared in 92.6% (126/136) of the patients, of whom 69.8% (88/126) had AUC24/MIC values greater than 80.Conclusion: Hematological indicators should be carefully monitored during LZD treatment, especially thrombocytopaenia and low hemoglobin, and a continuous period of monitoring after LZD withdrawal is also necessary. Since the AUC24 cut-off values for laboratory adverse events were relatively low, a trade-off is necessary between the level of drug exposure required for treatment and safety, and the exposure target (AUC24/MIC) in pediatric patients should be further studied, especially for patients with complications and concomitant medications.

Background The KMT2A gene, formerly named the MLL gene, is rearranged ( KMT2A r) in 70–75% of infants, 5–6% of children and 10–15% of adult patients with B cell acute lymphoblastic leukemia (B-ALL). The outcome after chemotherapy of pediatric cases remains poor, and only a few studies have investigated the clinical and laboratory features, treatment response and prognosis in Chinese populations. Methods A total of 48 B-ALL children with KMT2A r were enrolled in the study, and clinical and laboratory data were collected and analyzed by age group. The relationship between prognosis and traditional risk factors and treatment response was investigated for these patients who received chemotherapy. Results The 48 enrolled patients included 28 males and 20 females; 18 (37.50%) or 30 (62.50%) patients were an age of < 12 m (infant B-ALL) or of > 12 m at onset. An initial WBC count of 300 × 10 9 /L was detected in 7 (14.58%) patients; testicular leukemia (TL) or central nervous system involvement was found in 5 (10.41%) or 3 (6.25%) patients, respectively. Statistical differences were not found in the age groups of sex or initial WBC count, whereas TL was more common in the infant group ( P < 0.05). 11q23 was detected in 18 patients; KMT2A r was detected in 46 (95.83%) or 45 (93.75%) patients by FISH or multiplex RT–PCR technology, respectively; RNA-seq data were obtained for 18 patients, and 3 patients with uncommon KMT2A r were identified. KMT2A-AFF1 , KMT2A-MLLT3 and KMT2A-MLLT1 were the most common transcripts. Statistical differences were not found in treatment response by age groups, including dexamethasone induction, bone marrow (BM) smear status and minimal residual disease (MRD) level at different time points (TP), treatment-related mortality (TRM), or complete remission (CR) rate ( P > 0.05); MRD levels monitored by FCM or PCR were unequal at the same TP. Four patients died of treatment, and TRM was 8.33%; 40 patients achieved CR, and the CR rate for the cohort was 83.33%. Seven patients quit, 15 patients relapsed, and the 5 yr cumulative relapse rate was 59.16 ± 9.16%; the 5 yr prospective EFS (pEFS) for patients who were included or excluded from the TRM group was 36.86 ± 8.48% or 40.84 ± 9.16%, respectively. Multivariate analysis for prognosis and hazard ratio was performed for 37 patients without TRM and revealed that an initial WBC count of > 300 × 10 9 /L and a positive level of FCM-MRD were strongly related to a poor outcome for B-ALL patients with KMT2A r ( P < 0.05).

目的 探讨儿童范可尼贫血(FA)的临床特征、基因特点及预后.方法 回顾性分析2012年1月-2019年9月在重庆医科大学附属儿童医院诊断的25例FA患儿的临床资料.结果 伴有先天畸形者9例(36％),所有患儿均发生骨髓衰竭,无患儿发生恶性肿瘤.有先天畸形的患儿治疗6月后病情更易进展.染色体断裂试验阳性率达55％(11/20).FANCA致病突变最常见(50％),其次为FANCP(17％).7例患儿进行了 HSCT,4例发生了肠道GVHD,接受全相合供体的患儿均恢复正常的造血功能.结论 FANCA突变致病最常见,伴有先天畸形者应积极治疗,移植后GVHD发生率偏高,有HSCT适应症的患儿应权衡利弊后做出选择,尽量选择全相合供体进行移植.

OBJECTIVETo explore the molecular genetic characteristics of children with B-cell acute lymphoblastic leukemia (B-ALL) and the application value of RNA-sequencing (RNA-seq).METHODSThe clinical and laboratory examination data of newly diagnosed B-ALL children who were given treatment in the Department of Hematology, Children's Hospital of Chongqing Medical University from May 2015 to April 2020 were collected and analyzed. All children were confirmed by bone marrow morphology, histochemical staining and flow cytometry, and the karyotype analysis, FISH, RT-PCR and RNA-seq detection were conducted.RESULTSThere were 71 males and 58 females with a median age of 50(8-190) months in 129 newly diagnosed children with B-ALL. The fusion gene was positive in 99 children (76.7%). A total of 86 leukemia related or possibly related gene mutations were detected, with a positive rate of 66.7%. There was no significant difference in the detection rates of ETV6-RUNX1, BCR-ABL1, TCF3-PBX1 and KMT2A rearrangements among FISH, RT-PCR and RNA-seq. Rare fusion genes were detected by RNA-seq, including 1 case of KMT2A-USP2, 4 cases of Ph-like related fusion genes, 5 cases of MEF2D rearrangement, 5 cases of PAX5 rearrangement, 3 cases of ZNF384 rearrangement, as well as several fusion genes whose significance were not clear or had not been reported in children with leukemia. Besides, children with ETV6-RUNX1 fusion gene had good response to induction of remission, while children with BCR-ABL1 and ZNF384 rearrangement had poor response, the remission rate of minimal residual disease was statistically significant compared with other types (P<0.05).CONCLUSIONRNA-seq can not only detect known fusion genes, but also discover new or rare fusion genes and gene mutations. The application of RNA-seq has important guiding significance for risk classification and precise targeted therapy of pediatric B-ALL.

Background and Aims: Hepatitis B vaccine is the most effective preventive measure against hepatitis B virus (HBV) infection. However, the risk of HBV breakthrough infection in fully immunized children (neonatal hepatitis B immunization) who receive immunosuppressive therapy and transfusion of blood components is not well characterized. In this real-world study, we aimed to investigate the immune protection conferred by neonatal hepatitis B vaccine in children with acute lymphoblastic leukemia (ALL) who were treated with immunosuppressive therapy and blood component transfusions. Methods: Children with ALL who had received all three doses of neonatal hepatitis B vaccine were included in this study. HBV seromarkers were detected before and after the initiation of immunosuppressive therapy. Results: A total of 1,011 children with ALL who were fully vaccinated against hepatitis B in infancy before the initiation of immunosuppressive therapy were eligible for inclusion. HBV infection was detected in four of 410 children (0.98%) with an HBsAg test after the initiation of immunosuppressive therapy. The median interval from treatment initiation was 19 months. Conclusions: Three doses of neonatal hepatitis B vaccine conferred adequate protection. In endemic regions, there is a low risk of HBV breakthrough infection in fully immunized children with immunosuppressive therapy.

Specific fusion genes play important roles as risk factors for strategic treatment in pediatric B-cell acute lymphoblastic leukemia (B-ALL), and the risk factors in patients without common fusion genes have not been well demonstrated. We collected and analyzed clinical and laboratory findings, treatment responses and outcomes in B-ALL patients without specific fusion genes. Whole-exome sequencing (WES) and/or RNA sequencing (RNAseq) data from bone marrow relapsed patients were also analyzed. 283 patients were enrolled in the study. Traditional elements and treatment responses at different time points (TPs) were evaluated to classify risk groups and adjust the treatment strategy. Treatment-related mortality was found in 11 (3.89%) patients, 49 (17.31%) patients relapsed, and the ten-year prospective event-free survival (pEFS) was 78.2±2.5%. Univariate analysis revealed that significant differences were not found in the pEFS of traditional risk factors, including sex, age, WBC count or chromosome status; good responses of BM smears at TP1 and minimal residual disease (MRD) levels at TP2 and TP3 were strongly associated with prolonged pEFS. Compared with the IR or the HR group, patients in the SR group presented with longer pEFS and a lower relapse rate. Multivariable analysis of outcomes and hazard ratios revealed that a positive MRD level was a key risk factor. WES or RNAseq was performed for BM relapse patients, and adverse and unreported genetic abnormalities were discovered. Favorable outcomes were acquired in the cohort. The study results showed that traditional risk factors and poor prednisone response were overcome by modified chemotherapy, and a positive MRD level was a key risk factor in these patients. NGS is needed to discover more risk-related molecular abnormalities.