BACKGROUND:The prognosis for aplastic anemia (AA) patients undergoing cyclosporine is variable; therefore, a prognostic model is needed to optimize stratified treatment strategies. METHODS:This observational retrospective cohort study included patients with AA who received immunosuppressive therapy with cyclosporine. A total of 437 patients were randomly assigned to the training cohort (n = 262) or the validation cohort (n = 175) at a ratio of 6:4. Independent prognostic factors were identified through univariate regression and collinearity screening, and the Cox regression model was used to construct a nomogram for prognosis prediction. ROC curves, calibration curves and DCA curves were used to evaluate the discrimination, calibration performance and clinical practicality of the models. RESULTS:A nomogram for predicting overall survival was constructed using 13 identified independent predictors. ROC curve analysis revealed that the AUC values for both the training and validation sets exceeded or approach 0.80, indicating good model discrimination. The calibration curve showed a high degree of consistency between the model prediction results and the actual observed values, and DCA confirmed the model's relevance in clinical decision-making. CONCLUSION:In this study, a new nomogram model for predicting the prognosis of children with AA was developed, providing a tool to support doctors in predicting early-stage patient prognosis and developing reasonable treatment plans. IMPACT STATEMENT:Cyclosporine is the cornerstone drug for immunosuppressive therapy in acquired aplastic anemia. Pediatric patients with acquired aplastic anemia exhibit variable outcomes following single-agent cyclosporine therapy. This study developed a prognostic prediction model for childhood aplastic anemia patients treated with cyclosporine monotherapy, providing a basis for the stratified management of aplastic anemia, with strong clinical applicability. This nomogram model has not been reported in studies on early prognosis prediction of childhood aplastic anemia.

Biallelic variants in the neuroblastoma amplified sequence (NBAS) gene have been associated with short stature, optic atrophy, and Pelger-Huët anomaly (SOPH) syndrome, infantile liver failure syndrome type 2 (ILFS-2), and an increasingly broad spectrum of clinical phenotypes. However, cases presenting with hemophagocytic lymphohistiocytosis (HLH) accompanied by immune dysfunction and multisystem involvement have not been reported. We identified novel compound heterozygous variants in the NBAS gene, c.5139-5T>G and c.5983C>T, in a Chinese girl who successively developed recurrent infections, short stature, ILFS-2, progressive cytopenias from leukopenia to bicytopenia and eventually pancytopenia, and HLH. Polymerase chain reaction confirmed that c.5139-5T>G variant caused aberrant splicing. The c.5983C>T variant is novel and was classified as likely pathogenic according to American College of Medical Genetics and Genomics guidelines. Western blotting of the patient’s PBMCs detected only a truncated NBAS protein, consistent with the product predicted from the c.5983C>T variant. Functional studies in HEK293T cells overexpressing the truncated NBAS protein further indicated impaired NBAS function, as assessed by real-time quantitative reverse transcription polymerase chain reaction and immunofluorescence analysis. We systematically reviewed 322 previously reported patients and analyzed genotype–phenotype correlations in 316 cases to further define the clinical spectrum of NBAS-related disease. We identified a novel pathogenic NBAS variant, further expanded the phenotypic spectrum of NBAS-related disease, and provided additional insight into genotype–phenotype correlations. Pancytopenia and HLH may reflect severe immune dysregulation and poor prognosis, highlighting the importance of early recognition and timely intervention.

BACKGROUND:T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that remains a clinical challenge because of drug resistance and relapse, necessitating deeper insights into the mechanism of leukemogenesis and progression. Connexin 43 (CX43) modulates tumor growth and metastasis by regulating cell-extracellular matrix interactions and the tumor microenvironment, but its role in T-ALL remains unclear. The study aims to investigate the changes in the expression of CX43 in the context of T-ALL, its effect on patient prognosis, and the underlying mechanisms. METHODS:To investigate the impact of CX43 on survival and relapse, this study retrieved databases to analyze the differential expression of CX43 between patients with T-ALL and healthy individuals, as well as its prognostic implications. Meanwhile, the CX43-overexpressing (CX43OE) and neurogenic locus notch homolog protein 1 (Notch1)-mutant plasmids were used to develop a primary T-ALL knock-in mouse model and investigate the effects of CX43 on T-ALL in vitro and in vivo. RESULTS:The overexpression of CX43 significantly promoted the development and progression of T-ALL and suppressed apoptosis by increasing the stemness of T-ALL cells through the upregulation of Rac family small GTPase 1 (RAC1) expression and the promotion of the phosphorylation of the protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3β) pathway. Targeting the AKT/GSK3β axis attenuated the stemness induced by CX43 overexpression. CONCLUSION:These findings suggest that targeting CX43-mediated pathways may help overcome leukemia stem cell-driven relapse and improve treatment outcomes in patients with T-ALL.

X-linked hyper-IgM syndrome (XHIGM) is a rare immunodeficiency for which allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option, yet large pediatric Chinese datasets are scarce. We retrospectively analyzed 71 boys with genetically confirmed CD40L deficiency who underwent allogeneic HSCT between 2009 and 2020 at eight centers in China. Median age at HSCT was 3 yr (range, 0.6 to 17), with 74.6% transplanted before age 5. Donors were mismatched unrelated (42.3%), matched unrelated (33.8%), matched sibling (18.3%), and haploidentical (5.6%). Peripheral blood was the predominant stem cell source (67.6%), followed by cord blood (31.0%). Myeloablative conditioning was used in 95.8%. Median times to neutrophil and platelet engraftment were 12 and 14 d, respectively. Primary graft failure occurred in 5.6%. Acute GVHD developed in 60.6% (grade III to IV, 11.3%), and chronic GVHD in 25.4% (none-severe). Cytomegalovirus and EBV-DNAemia occurred in 56.3% and 39.4%, respectively; post-transplant lymphoproliferative disorder developed in 4.2%. Other complications included sinusoidal obstruction syndrome and hemorrhagic cystitis (7.0% each). At last follow-up, 9 patients (12.1%) had died, mainly from infections (8.5%). At a median follow-up of 7.8 yr, the estimated 10-yr overall, disease-free, and GVHD-free survival rates were 85.91%, 64.79%, and 77.14%, respectively. Survival was superior in younger patients, those with lower body weight, and well-matched related or unrelated donors. Immune reconstitution showed early NK recovery with progressive T and B cell restoration over 1 yr. These data support HSCT as effective long-term therapy for XHIGM and highlight benefits of early timing and optimal HLA matching.

The outcomes of children with aplastic anemia receiving cyclosporine monotherapy vary significantly in terms of mortality risk; therefore, a prognostic model for predicting mortality risk was constructed to optimize risk-stratified treatment strategies. This retrospective cohort study included children with acquired AA receiving cyclosporine-based immunosuppression, stratified by disease severity (vSAA/SAA/NSAA) and randomly split into training (70

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition predominantly affecting children, characterized by hyperinflammation and high early mortality. While the HScore criteria, developed by Fardet et al. in 2014, have been widely used to diagnose HLH, recent studies have also explored its potential to predict disease severity in COVID-19 patients, with findings indicating that higher HScore values correlate with increased mortality risk and may identify patients who could benefit from immunomodulatory treatment.However, the potential of HScore-related indicators in predicting early prognosis in patients with HLH has not been reported. This study aimed to investigate the association between HScore scores and related indicators and early mortality in children with Hemophagocytic Lymphohistiocytosis (HLH), and to develop a Cox prediction model for early mortality based on optimized HScore parameters to assist medical professionals in better risk stratification at the time of diagnosis. This retrospective study included 624 children diagnosed with HLH admitted to the Children's Hospital of Chongqing Medical University between January 2006 and December 2022. Five Cox prediction models were developed: Model 1 used HScore values; Model 2 used original HScore grouping criteria; Model 3 used raw HScore parameters; Model 4 grouped HScore parameters by optimal cut-offs; Model 5 combined optimized HScore parameters with common prognostic indicators (total protein, TC, APTT, BUN, ferritin). Model performance was assessed using AUC and calibration curves. An interactive web application was developed using R and Shiny for clinical use. The optimal cut-off value for the HScore was determined to be 223, which stratified children into high-risk and low-risk groups. The estimated 30-day survival rates were 77.9% (95% CI: 73.6%-82.5%) for the low-risk group and 65.8% (95% CI: 60.5%-71.7%) for the high-risk group (P < 0.001). Model 5 demonstrated the highest AUC on both training and validation datasets, with values of 0.881 (95% CI: 0.818-0.942) and 0.813 (95% CI: 0.747-0.881), respectively. Factors associated with increased early mortality risk included hemoglobin levels <61 g/L, platelet counts <31×10^9/L, ferritin levels ≥1318 ng/mL, total protein levels ≥52.3 g/L, AST levels >460 U/L, total cholesterol levels <3.23 mmol/L, APTT levels >60.2s, and bone marrow phagocytosis. To facilitate clinical application, we developed a free online calculator tool (https://ranwyr.shinyapps.io/DynNomapp/) based on the optimal model results. The HScore alone is insufficient for accurately predicting early mortality risk in children with HLH. Our study provides a novel early mortality prediction tool based on optimized HScore parameters, which may aid clinicians in better risk stratification and decision-making at the time of diagnosis.

Background:Post-transplant infections are common complications, and the reasons are pre-transplant conditioning, time required for post-transplant immune reconstitution, and use of immunosuppressive agents. We aimed to analyze the risk factors for Epstein-Barr virus (EBV) reactivation and its progression to post-transplant lymphoproliferative disorder (PTLD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children and to determine the EBV PCR diagnostic threshold for PTLD. Methods:We retrospectively analyzed clinical data of 309 patients who underwent allo-HSCT without engraftment failure at the Children's Hospital of Chongqing Medical University from January 1, 2016, to December 21, 2021. The occurrences of EBV reactivation and PTLD were also recorded. The risk factors for EBV reactivation and progression to PTLD were analyzed, and the diagnostic threshold for PTLD was determined using whole-blood EBV PCR. Results:Among 309 pediatric patients, 256 experienced EBV reactivation within one year and 12 progressed to PTLD. Univariate and multivariate analyses indicated that ATG was the independent risk factor for EBV reactivation. Grade III-IV acute graft-vs.-host disease (aGVHD) was the risk factor for PTLD after EBV reactivation. Conclusions:Post-transplant EBV reactivation is a common complication after allo-HSCT, but rarely progresses to PTLD. Identification of the risk factors for PTLD and regular monitoring of the EBV-DNA load play important roles in prevention and cure of PTLD after HSCT.

Autoimmune cytopenia (AIC) following pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT) is relatively rare but it is a challenging complication, and standardized treatment guidelines are lacking. We retrospectively analyzed 436 pediatric patients undergoing allo-HSCT; 37 (8.5%) developed AIC, characterized by autoimmune hemolytic anemia (n = 13), immune thrombocytopenia (n = 11), and Evans syndrome (n = 13). Risk factor analysis revealed that younger age at HSCT, nonmalignant diseases, unrelated donor transplantation, and chronic graft-versus-host disease (cGVHD) were significantly associated with the development of AIC. Through multivariate analysis, cGVHD was identified as an independent risk factor for AIC. In our study, the first-line treatment for AIC involved steroids and/or intravenous immunoglobulin, with a complete remission rate of 48.6%. Additional therapeutic strategies included rituximab, which led to complete remission in 5 of 12 patients we treated, and sirolimus, with 3 of 7 patients achieving complete remission. Three patients achieved partial remission, while 9 patients died due to complications, such as severe infections, extensive GVHD, and multiorgan bleeding. Our findings suggest that cGVHD is an independent risk factor for post-transplant AIC and is typically associated with adverse outcomes, highlighting the critical importance of timely and effective interventions.

Background Acute lymphoblastic leukemia (ALL) represents the most prevalent pediatric malignancy. The Chinese Children's Cancer Group for ALL (CCCG-ALL) constitutes China's largest collaborative pediatric ALL treatment consortium. From 2015 to 2020, 7,640 pediatric ALL cases were treated under the CCCG-ALL protocol, achieving a 5-year overall survival (OS) of 91% and event-free survival (EFS) of 80%. Current HSCT recommendations are limited to relapsed patients, TCF3::PBX1-positive cases, and select high-risk MLL-rearranged infant leukemias.Objective To evaluate the efficacy and appropriateness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) indications within the CCCG-ALL-2015 protocol and identify key prognostic determinants affecting transplantation outcomes.Methods We retrospectivly analyzed pediatric patients who received allo-HSCT between January 1, 2015, and December 31, 2019 across 20 collaborating hospitals in China. Of 7,640 patients treated under CCCG-ALL-2015, 378 (4.95%) underwent allo-HSCT, with complete transplant data available for 313 patients. Survival analyses employed Kaplan-Meier methodology with Log-rank comparisons. Prognostic variables were evaluated using Cox proportional hazards modeling.Results Among 313 children (209 males, 104 females), B-ALL predominated with 269 cases versus 44 T-ALL cases. Median follow-up duration was 2.02 years (range: 0.02-6.67 years). Five-year OS and EFS were 60.8% and 56.1%, respectively, with cumulative relapse incidence of 26.6% and treatment-related mortality of 14.1%. Among 124 high-risk patients meeting CCCG-ALL-2015 criteria, only 30 underwent HSCT at first complete remission (CR1) according to protocol recommendations, achieving superior 5-year OS compared to chemotherapy-only or transplantation at second or later remissions (≥CR2) cohorts (65.4% vs. 52.2% vs. 45.5%). Notably, 20 patients underwent HSCT at non-remission (NR) or partial remission (PR) status, still with approximately half achieving long-term survival (5-year OS: 47.6%; EFS: 40.0%). Donor distribution comprised haploidentical (n=204, 65%), matched unrelated (n=89, 28%), and matched related donors (n=20, 6%). Survival outcomes remained comparable between haploidentical and non-haploidentical donors (OS: 60.9% vs. 61.9%, P=0.91; EFS: 57.3% vs. 55.5%, P=0.40), with similar acute GVHD incidence (58.21% vs. 53.21%, P=0.41). However, haploidentical HSCT was associated with reduced relapse rates (18.9% vs. 29.5%, P=0.032) but increased chronic GVHD incidence (39.3% vs. 25%, P=0.03), predominantly moderate-to-severe forms (60.76% vs. 30.71%, P=0.013). Grade IV aGVHD significantly compromised 5-year OS (26.9% vs. 64.5%, P<0.001), primarily due to infection-related mortality (18/19 cases, 94.7%). Conversely, mild cGVHD correlated with superior outcomes compared to absent, moderate, or severe cGVHD (5-year OS: 77.1% vs. 62.3%, 64.7%, 30.7%, P<0.001; EFS: 75.1% vs. 56.4%, 61.1%, 25.3%, P<0.001). Multivariable analysis revealed no significant survival impact from gender, immunophenotype, risk stratification, fusion genes, number of remissions prior to HSCT, pre-transplant MRD status, conditioning, GVHD prophylaxis, or donor type (all P>0.05). Among 39 Ph-positive patients, all achieved complete remission (CR). HSCT at CR1 showed superior 5-year OS (90%) compared to ≥CR2 HSCT (59.7%) and non-HSCT cohorts with end-of-induction MRD-negative (77.32%) or MRD-positive (59.47%) status, though differences were not statistically significant.Conclusion CCCG-ALL-2015 HSCT indications for pediatric ALL demonstrate clinical validity, with high-risk patients deriving transplantation benefit. Importantly, even patients unable to achieve CR may still benefit from HSCT, as evidenced by 40% long-term survival in NR/PR patients, suggesting expanded therapeutic potential beyond current recommendations. Mild cGVHD confers survival advantage in transplant recipients. Philadelphia chromosome-positive patients with persistent MRD may particularly benefit from HSCT at CR1. Extended follow-up periods and larger patient cohorts are essential to validate these findings and refine transplantation criteria.

BackgroundThe genetic variations in aplastic anemia (AA) patients are closely related to clonal hematopoiesis, but there is limited research on this topic in children with AA. The aim of this study is to investigate the molecular classification and outcomes of children with AA combined with myeloid neoplasm-associated gene variants.MethodsThe clinical features, types of gene variants, mechanisms of action of the mutated genes, and correlations between gene variants and the outcomes of AA patients with myeloid neoplasm-associated gene variants were retrospectively analyzed.ResultsForty-six AA patients with myeloid neoplasm-associated gene variants were included, and a total of 20 gene variants were identified. The most frequent variant affected TET2 (9 patients, 19.6%), followed by ASXL1 (5 patients, 10.9%) and MPL (5 patients, 10.9%). Other variants, in descending order, affected TERT (4 patients); SH2B3, FLT3, ETV6, and JAK2 (3 patients each); BCOR, BCORL1, TP53, KIT, and SF3B1 (2 patients each); and CALR, GATA2, RUNX1, CBL, IDH1, IDH2, and WT1 (1 patient each). Six patients had 2 gene variants. The original mechanisms of action of the mutated genes mainly involved epigenetics and signal transduction pathways; both groups of genes were affected in 39.1% (18/46) of the patients. The difference in the efficacy of immunosuppressive therapy (IST) among the different gene groups was not significant. Disease severity (P = 0.046) and hematological response at 3 months (P = 0.002), 6 months (P = 0.001), 9 months (P = 0.001), and 1 year (P = 0.001) were important factors affecting survival time, but genotype was not. None of the patients experienced clonal evolution by the end of the follow-up cut-off time.ConclusionIn patients with AA combined with myeloid tumor neoplasm-associated gene variants, TET2, ASXL1 and MPL variants were the most frequently observed and primarily involved epigenetics and signal transduction pathways. There was no significant difference in the efficacy of IST among patients with different gene variants. Survival time was associated with disease severity, and the development of a hematological response—particularly when achieved at 3 months—was an independent key factor, whereas genotype was not.

Background:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment for β-thalassemia major (TM). Currently, TM patients undergoing allo-HSCT achieve a survival rate exceeding 90%, with over 80% attaining disease-free survival following treatment at transplant centers worldwide. Sibling donors constitute the most common graft source, and the immune status of pediatric recipients directly influences transplant approach selection, conditioning regimen design, and prognosis. Children with TM exhibit distinct immune states before and after transplantation, yet research on post-transplant immune reconstitution in these patients remains limited. Therefore, this study aims to explore the characteristics of immune reconstitution following allo-HSCT in TM patients, with the goal of providing additional valuable insights for clinical management. This study aimed to investigate the differences in lymphocyte subset reconstitution within 1 year after allo-HSCT in children with TM, evaluate the efficacy of transplantation, and explore factors influencing post-transplant immune cell reconstitution. Methods:We retrospectively analyzed the clinical data of 74 children with TM who underwent allo-HSCT from September 2014 to December 2020 at the Transplantation Center of the Department of Hematology and Oncology, Children's Hospital of Chongqing Medical University to investigate the factors influencing the reconstitution of immune cells after transplantation in children with TM. Results:(I) The results showed that post-transplant cytomegalovirus (CMV) infection, CD34+ cell content in the graft, and donor type could influence the level of immune cell reconstitution after transplantation in children with TM. (II) The level of post-transplant cell reconstitution was higher in children who did not have anemic heart disease before transplantation, who were compatible human leukocyte antigen (HLA) 10/10 transplants, who were donor-recipient blood group compatibility, and who did not have acute graft-versus-host disease (aGVHD) after transplantation. (III) CMV-infection-positive and Epstein-Barr virus (EBV)-infection-positive children had higher levels of T-cell reconstitution, and CMV-infection-negative children had higher levels of NK-cell and B-cell reconstitution. Conclusions:(I) Post-transplant CMV infection, CD34+ cell content in the graft, and donor type were independent influences on the level of T- and B-cell reconstitution after transplantation in children with TM. (II) No anemic heart disease before transplantation, donor-recipient blood type compatibility, no aGVHD after transplantation, no cGVHD after transplantation, and HLA 10/10 compatible transplantation are favorable for immune cell reconstitution after transplantation. (III) CMV infection and EBV infection after transplantation favored T-cell reconstitution, while CMV infection was detrimental to B-cell reconstitution.

Kenny-Caffey syndrome (KCS) is a rare genetic disorder characterized by extreme short stature, cortical thickening and medullary stenosis of tubular bones, facial dysmorphism, abnormal T cell function, and hypoparathyroidism. Biallelic loss-of-function variants in TBCE cause autosomal recessive type 1 KCS (KCS1). By contrast, heterozygous missense variants in a restricted region of the FAM111A gene have been identified in autosomal dominant type 2 KCS (KCS2) and a more severe lethal phenotype, osteocraniostenosis (OCS); these variants have recently been shown to confer a gain of function. In this study, we describe 2 unrelated children with KCS and OCS who were homozygous for different FAM111A variant alleles that result in replacement of the same residue, Tyr414 (c.1241A>G, p.Y414C and c.1240T>A, p.Y414N), in the mature FAM111A protein. Their heterozygous relatives are asymptomatic. Functional studies of recombinant FAM111AY414C demonstrated normal dimerization and a mild gain-of-function effect. This study provides evidence that both biallelic and monoallelic variants of FAM111A with varying degrees of activation can lead to dominant or recessive KCS2 and OCS.

BackgroundTumor lysis syndrome (TLS) often occurs early after induction chemotherapy for acute lymphoblastic leukemia (ALL) and can rapidly progress. This study aimed to construct a machine learning model to predict the risk of TLS using clinical indicators at the time of ALL diagnosis.MethodsThis observational cohort study was conducted at the National Clinical Research Center for Child Health and Disease. Data were collected from pediatric ALL patients diagnosed between December 2008 and December 2021. Four machine learning models were constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) to select key clinical indicators for model construction.ResultsThe study included 2,243 pediatric ALL patients, and the occurrence of TLS was 8.87%. A total of 33 indicators with missing values ≤30% were collected, and 12 risk factors were selected through LASSO regression analysis. The CatBoost model with the best performance after feature screening was selected to predict the TLS of ALL patients. The CatBoost model had an AUC of 0.832 and an accuracy of 0.758. The risk factors most associated with TLS were the absence of potassium, phosphorus, aspartate transaminase (AST), white blood cell count (WBC), and urea levels.ConclusionWe developed the first TLS prediction model for pediatric ALL to assist clinicians in risk stratification at diagnosis and in developing personalized treatment protocols. This study is registered on the China Clinical Trials Registry platform (ChiCTR2200060616).Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2200060616.

Objective:Gut acute graft-versus-host disease (aGVHD) is one of serious complication after hematopoietic stem cell transplantation (HSCT). Mucosal-associated invariant T (MAIT) cells are a group of innate T cells that are enriched in the gut. Currently, there is limited research on the role and function of MAIT cells in the development of aGVHD in humans.Our study aim to investigate the effect of MAIT cells on the occurrence of gut aGVHD after HSCT in children, and to developing a new clinical prevention and treatment strategy for gut aGVHD. Methods: We collected peripheral blood(PB)samples from 81 patients 30 days after HSCT. The content of MAIT cells was detected via flow cytometry to investigate the relationship between MAIT cells and gut aGVHD occurrence in children. Results: The count of MAIT cells in the PB of children with gut aGVHD was notably lower than that in those without aGVHD and other types of aGVHD. Conclusion: The PB of patients who develop gut aGVHD after HSCT demonstrates a reduction in MAIT cells. This reduction may be associated with delayed immune reconstitution and a higher risk of gut aGVHD post-transplantation,as well as a potential impact on the host's capacity to defend against intestinal infections.

OBJECTIVES:To investigate the cumulative incidence of recurrence (CIR) in children with acute lymphoblastic leukemia (ALL) after treatment with the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol and the risk factors for recurrence. METHODS:A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019. CIR was calculated, and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia (B-ALL) were analyzed. RESULTS:Among the 852 children with ALL, 146 (17.1%) experienced recurrence, with an 8-year CIR of 19.8%±1.6%. There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group (P>0.05). For the 146 children with recurrence, recurrence was mainly observed in the very early stage (n=62, 42.5%) and the early stage (n=46, 31.5%), and there were 42 children with bone marrow recurrence alone (28.8%) in the very early stage and 27 children with bone marrow recurrence alone (18.5%) in the early stage. The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene (HR=4.177, 95%CI: 2.086-8.364, P<0.001) and minimal residual disease≥0.01% on day 46 (HR=2.013, 95%CI: 1.163-3.483, P=0.012) were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol. CONCLUSIONS:There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol, mainly bone marrow recurrence alone in the very early stage and the early stage, and minimal residual disease≥0.01% on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

BackgroundWHIM syndrome is a rare, autosomal dominant inborn error of immunity characterized by warts, hypogammaglobulinemia, infection, and myelokathexis. It is caused mainly by heterozygous mutations at the C-terminus of the C-X-C chemokine receptor type 4 (CXCR4) gene.MethodsWe described the detailed clinical, genetic, immunological and treatment characteristic of four WHIM patients from a single Chinese family.ResultsHere, we report four patients from a family carrying a variant of CXCR4 (c.1016_1017dupCT), which introduces a frameshift at codon V340, resulting in an extension of 14 amino acids (p.V340L fs*27). We provide and in-depth analysis of their clinical, genetic, immunological and treatment characteristic, noting that these patients exhibited an atypical clinical phenotype when compared to reported CXCR4R334X patients. Additionally, the frameshift variant CXCR4V340fs led to impaired receptor downregulation in patients’ PBMCs, and in HEK293T cells transfected with the variant plasmids.ConclusionsOur study provided detailed clinical features of four CXCR4V340fs WHIM patients from one Chinese family who presented atypical phenotype and enrich the spectrum of WHIM syndrome.

Objective:To explore the gene mutations of Langerhans cell histiocytosis in children,and to analyze the correlation of BRAF V600E mutation with clinical features and prognosis of LCH,so as to provide reference for clinical diagnosis and treatment. Methods:Fluorescence PCR was used to detect gene mutations in paraffin-embedded tissue samples from 78 children with LCH,and the correlation of BRAF V600E mutation with clinical characteristics and prognosis of LCH in children was analyzed. Results:Among the 78 children,41 cases (52.6％) had BRAF V600E mutation,8 cases (10.3％) had MAP2K1 mutation,1 case (1.3％) had BRAF Exon 12 mutation,1 case (1.3％) had ARAF mutation,and 1 case (1.3％) had PIK3CA mutation. BRAF V600E mutation was not significantly correlated with sex,age,multisystem involvement,risk-organ involvement,CNS-risk lesions,and early treatment response in children with LCH (P>0.05),and it was also not significantly correlated with the recurrence and event-free survival (EFS) of children with LCH (P>0.05). Conclusion:LCH is an inflammatory myeloid tumor. BRAF V600E mutation is not correlated with clinical features,early treatment response,recurrence and prognosis of LCH.

OBJECTIVE:To analyze the efficacy and influencing factors of cyclosporine (CsA) alone in the treatment of children with acquired aplastic anemia (AA). METHODS:The clinical data of children diagnosed with AA and treated with CsA alone from January 1, 2016 to December 31, 2020 in the Children's Hospital of Chongqing Medical University were collected, and the efficacy and influencing factors of CsA treatment were evaluated. RESULTS:Among the 119 patients, there were 62 male and 57 female, with a median age of 7 years and 1 month. There were 45 cases of very severe AA (VSAA), 47 cases of severe AA (SAA), and 27 cases of non-severe AA (NSAA). At 6 months after treatment, the efficacy of VSAA was lower than that of SAA and NSAA, and there was a statistical difference (P < 0.01). 6 cases died early, 16 cases relapsed, 2 cases progressed to AML and ALL. The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA, while high PLT count was a protective factor (P =0.008, P =0.002). The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5×109 /L, 68.5%, respectively. Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST (P =0.020, OR =0.062), and high PLT count was a protective factor (P =0.044, OR =1.038). At 3 months of treatment, CsA response and NSAA were the risk factor for recurrence (P =0.001, 0.031). CONCLUSION:The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone. A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA, and a high proportion of bone marrow lymphocyte was an unfavorable factor. CsA response at 3 months and NSAA were risk factors for recurrence.

Mitochondria are key regulators of hematopoietic stem cell (HSC) homeostasis. Our research identifies the transcription factor Nynrin as a crucial regulator of HSC maintenance by modulating mitochondrial function. Nynrin is highly expressed in HSCs under both steady-state and stress conditions. The knockout Nynrin diminishes HSC frequency, dormancy, and self-renewal, with increased mitochondrial dysfunction indicated by abnormal mPTP opening, mitochondrial swelling, and elevated ROS levels. These changes reduce HSC radiation tolerance and promote necrosis-like phenotypes. By contrast, Nynrin overexpression in HSCs diminishes irradiation (IR)-induced lethality. The deletion of Nynrin activates Ppif, leading to overexpression of cyclophilin D (CypD) and further mitochondrial dysfunction. Strategies such as Ppif haploinsufficiency or pharmacological inhibition of CypD significantly mitigate these effects, restoring HSC function in Nynrin-deficient mice. This study identifies Nynrin as a critical regulator of mitochondrial function in HSCs, highlighting potential therapeutic targets for preserving stem cell viability during cancer treatment.