Background: Few large-scale cohort studies have reviewed consecutive cases of thrombotic microangiopathy (TMA), especially in children. Objectives: The aim of our study was to evaluate causes and outcomes of TMA at a tertiary pediatric center in China over a 9-year period. Methods: We retrospectively analyzed consecutive pediatric TMA patients admitted to Beijing Children's Hospital from December 2015 to January 2025. The primary endpoint was death or progression to kidney failure. Multivariable Cox regression identified independent predictors of this composite endpoint. Results: We retrospectively analyzed 303 consecutive pediatric patients with a first episode of TMA. Secondary TMA was the most common type (n = 172; 57%), followed by atypical hemolytic uremic syndrome (n = 93; 31%), thrombotic thrombocytopenic purpura (n = 24; 8%), and Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (n = 14; 5%). Among the 172 cases of secondary TMA, the most common causes were hematopoietic stem cell transplantation (n = 95; 55%) and systemic diseases (n = 40; 23%). After a median follow-up of 35 months, death or kidney failure occurred in 53 (31%), 7 (8%), 1 (4%), and 0 patients with secondary TMA, atypical hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome, respectively. Multivariate Cox regression showed that secondary TMA (hazard ratio [HR], 3.57; 95% CI, 1.53-8.30; P < .01), the presence of heart failure and/or shock at onset (HR, 2.21; 95% CI, 1.24-3.93; P = .01), and the need for mechanical ventilation support due to respiratory failure (HR, 3.88; 95% CI, 2.19-6.88; P < .001) were independent risk factors for death or kidney failure. Conclusion: This study shows that secondary TMA is the predominant form of pediatric TMA. Secondary TMA, heart failure/shock, and the requirement for mechanical ventilation were identified as independent risk factors for death or kidney failure in children.

BACKGROUND:The incidence of pediatric venous thromboembolism (VTE) has been increasing in recent years. Due to the unique hemostatic characteristics of children, thrombi are often difficult to resolve once formed and may result in long-term sequelae. Rivaroxaban has been approved for the treatment of pediatric VTE; however, real-world data on its use in Chinese pediatric populations remain limited. OBJECTIVES:This study aimed to evaluate the effectiveness and long-term safety of rivaroxaban in children with VTE and to provide real-world evidence to support its clinical use. METHODS:This single-center retrospective observational study included children aged >28 days and <18 years who were diagnosed with VTE and received rivaroxaban treatment for at least one month at Beijing Children's Hospital between January 2022 and April 2025. Demographic characteristics, clinical data, and treatment information were collected. Effectiveness outcomes included thrombus resolution and changes in thrombus burden assessed by imaging. Safety outcomes included bleeding events and adverse drug reactions. All patients were followed up for 3 months during treatment, with an additional 3 months of subsequent follow-up. RESULTS:A total of 189 pediatric patients with VTE treated with rivaroxaban were included between January 1, 2022 and April 1, 2025. The median age was 8.6 years, and 53.97% were male. The most common VTE risk factor was pulmonary disease (pneumonia) (58.20%), followed by catheter-related thrombosis (33.33%). At 3-month follow-up, complete thrombus resolution was achieved in 24.34% of patients, partial improvement in 57.67%, and no improvement in 14.29%. Thrombus recurrence occurred in 2.12% of patients, with no fatal VTE or death observed. Univariable logistic regression showed no significant predictors of thrombus recanalization (all P > 0.05). No significant difference in efficacy was found between patients with and without cancer (P = 0.148). For safety, bleeding events were rare and mostly mild (4.79% clinically relevant non-major bleeding), with one discontinuation due to melena and no fatal or intracranial hemorrhage. No significant risk factors for bleeding were identified in univariable analysis. CONCLUSIONS:In this real-world pediatric cohort, rivaroxaban demonstrated favorable effectiveness and an acceptable safety profile, consistent with findings from previous clinical trials. Larger multicenter real-world studies are warranted to further define the clinical value of rivaroxaban in pediatric VTE.

BackgroundPredictors for the successful eradication of neutralizing anti-FVIII alloantibodies (inhibitors) in hemophilia A patients receiving immune tolerance induction (ITI) therapy remain limited. Maternal microchimerism (MMc) showed potential to protect hemophilia A patients from inhibitor development.ObjectivesTo investigated the role of MMc in ITI therapy.Patients/MethodsThis observational study enrolled 121 pediatric with hemophilia A and inhibitors. MMc was determined using droplet digital PCR. Low-dose ITI (FVIII ~50IU/kg every other day) was administered, with adjunctive rituximab given to patients with higher risk clinical features.ResultsOf the 101 patients evaluable for MMc, 88 completed ITI, 18 were MMc positive (MMc+) and 70 were MMc negative (MMc-). Success was achieved in 75 (85.2%) patients, including 16 of 18 MMc+ patients (88.9%) and 59 of 70 MMc- patients (84.3%). Compared with MMc- patients, MMc+ patients had a lower peak inhibitor during ITI (median, 5.3 vs. 37.8 BU/ml, p = 0.029), less frequent rituximab use (27.8% vs. 61.4%; p = 0.011), and a shorter time to ITI success (median, 3.0 vs 9.9 months; p = 0.009). Multivariate Cox regression identified MMc+ (HR = 2.770), pre-ITI inhibitor <10BU/ml (HR = 2.663), peak inhibitor during ITI<200BU/ml (HR = 4.954) and non-large deletion/duplication F8 mutations (HR = 2.344) as independent predictors of shorter time to ITI success.ConclusionMMc was associated with more rapid ITI success in children with hemophilia A and inhibitors receiving low-dose ITI regimen, suggesting the potential role of MMc in facilitating the eradication of FVIII inhibitors.

Objectives Antithrombin (AT) is a critical anticoagulant whose deficiency, which is common in many clinical conditions, requires precise management, although accurate laboratory measurements of low AT levels are challenging. This study aims to evaluate the precision and comparability of AT activity assays across different analytical systems, particularly at low activity levels, with the goal of developing validated optimization strategies to improve performance and interlaboratory harmonization. Methods Standardized lyophilized plasma materials (with AT activities of 10%, 15%, 35% and 100% of normal) were distributed to nine clinical laboratories via Systems A and B, with bovine thrombin as the reagent, and System C, with bovine activated coagulation factor Ⅹ as the reagent. Baseline performance was assessed through a laboratory evaluation and external quality assessment style comparison. Optimization measures (standardized reagent reconstitution, calibration curves at low levels, enhanced quality control protocols) were then applied in laboratories with better baseline performance, followed by a re-evaluation study to assess improvements. Results The initial evaluation confirmed significant variability at low AT activity levels: Systems A and B demonstrated closer agreement with target levels, whereas System C exhibited significant bias and poor reproducibility and was consequently excluded from optimization. After implementation of the optimization protocols, low-level AT activity measurements showed markedly reduced bias and improved precision. At the 10% and 15% levels, both the interlaboratory coefficients of variation and the recovery rates significantly improved. In the re-evaluation study, Systems A and B demonstrated enhanced performance across all participating laboratories. Conclusions: This multicenter evaluation established the feasibility of significantly improving AT activity assay performance through targeted methodological optimization. Through the use of quality control materials and harmonized procedures, the method achieved reliable low-level activity measurements, thereby paving the way for the reliable clinical application of AT activity measurements.

Background Emicizumab has markedly improved bleed prevention in hemophilia A, but its high cost remains a challenge, especially in resource-constrained settings. Many regions are now exploring dose reduction strategies to alleviate financial burden. However, empirical dose minimization without clear guidance may risk inadequate hemostatic protection and breakthrough bleeding. While standard weight-based dosing ensures efficacy, a personalized, pharmacokinetic/pharmacodynamic (PK/PD)-guided dosing strategy may reduce treatment burden without compromising bleed protection. Evidence supporting such individualized approaches in real-world remains limited. Objective This study aimed to evaluate the feasibility, safety, and preliminary effectiveness of PK/PD-guided emicizumab dose reduction in Chinese pediatric patients with hemophilia A, following an initial period of standard prophylaxis. Methods This was a prospective, single-center observational study conducted in a real-world clinical setting. Children under 18 years of age with severe congenital hemophilia A, either with or without FVIII inhibitors, who had received standard emicizumab prophylaxis for at least 12 months, were enrolled. After this observation period, patients and their caregivers were offered the option to transition to a reduced dosing regimen guided by individualized PK and PD targets. Emicizumab concentrations were measured using a modified one-stage clotting assay, and FVIII-equivalent activity was assessed using a chromogenic assay (HYPHEN). Individual pharmacokinetic parameters were estimated based on the population PK model by Retout et al. (Clin Pharmacokinet. 2020). The dose adjustment aimed to maintain FVIII-equivalent activity between 10–15 IU/dL and emicizumab trough concentrations above 30 μg/mL (±10 μg/mL). Patients were prospectively followed for a minimum of 6 months after dose reduction, with systematic monitoring for bleeding events, thrombotic complications, and treatment-related adverse events. Results A total of 46 patients were enrolled in the study. Among them, 15 patients transitioned to the PK/PD-guided Individualized dose reduction strategy after completing 12 months of standard emicizumab therapy. The median age of this subgroup was 2.0 years, with a range from 0.9 to 16.3 years. Of the 15 patients, 13 were negative for FVIII inhibitors, 2 had a history of inhibitors. The median monthly emicizumab dose was reduced from 5.4 mg/kg (range: 3.2–6.2) to 3.2 mg/kg (range: 2.6–4.0). Correspondingly, the median trough concentration decreased from 48.5 μg/mL (range: 36.5–68.7) to 32.1 μg/mL (range: 27.0–38.4). Despite the dose reduction, FVIII-equivalent activity remained within the target range in most patients, with a median of 12.3 IU/dL (range: 12.0–18.5). Throughout the 6-month follow-up under reduced dosing, no bleeding events, thrombotic complications, or treatment-related adverse events were observed. In addition, joint ultrasound assessments performed before and after dose adjustment showed no evidence of new or progressive damage, suggesting preserved joint health throughout the reduced dosing period. Conclusion This prospective real-world study demonstrates that emicizumab dose reduction guided by PK/PD targets is feasible, safe, and effective in pediatric patients with hemophilia A after an initial period of standard prophylaxis. The individualized approach maintained excellent bleed protection while substantially reducing drug exposure. These findings highlight the potential of PK/PD-guided dosing to improve access and cost-efficiency of emicizumab in settings where treatment affordability is a concern. Larger-scale, multi-center studies with extended follow-up are needed to confirm these promising results and support broader adoption of this strategy.

Hemophilia A is a rare inherited bleeding disorder typically managed with coagulation factor VIII (FVIII) replacement therapy. Designing personalized prophylactic regimens requires accurate pharmacokinetic (PK) characterization; current population PK (popPK) and Bayesian approaches provide a principled framework for individualized dosing, but their routine clinical implementation may still be constrained by model specification requirements and practical considerations in data collection and analysis. Here we present a machine learning (ML) framework, incorporating state-of-the-art language models, to predict individual FVIII PK parameters in pediatric patients. Using minimal sampling and routinely collected clinical data, our approach achieves superior performance over the widely adopted WAPPS-Hemo platform in predicting in vivo recovery (IVR) and FVIII half-life. These findings highlight the potential of AI-driven methods to reduce patient burden while improving accuracy in individualized treatment planning for children with severe hemophilia A.

Background and Objective: Avatrombopag is a thrombopoietin receptor agonist that has demonstrated clinical efficacy in rapidly increasing platelet counts and achieving bleeding control in children with chronic immune thrombocytopenia. Early prediction of treatment response is critical for reducing unnecessary drug exposure and guiding personalized treatment strategies. However, accurate prediction remains challenging due to the inherent characteristics of clinical tabular data, including missing values caused by inconsistent data recording, small sample size, and high-dimensional clinical features. This study aims to develop an effective computational framework for early prediction of treatment response under these conditions. Methods: We propose a multi-view learning framework that constructs multiple views by applying diverse imputation methods to the same dataset, with each view capturing unique assumptions about missingness. A feature selection encoder is employed to reduce feature redundancy and improve model interpretability. Multi-view fusion and co-regularization are integrated at the prediction level to learn complementary patterns across different views. In addition, contrastive learning is introduced to alleviate the small data problem and enhance representation robustness. Results: Experiments on real-world clinical data of children treated with avatrombopag demonstrate that the proposed method consistently outperforms multiple competitive baseline models in predicting treatment response. Conclusions: This study provides a practical and interpretable multi-view learning framework for early identification of treatment response in chronic immune thrombocytopenia, supporting more personalized and efficient treatment decisions in pediatric hematology.

Immune thrombocytopenia (ITP) is an autoimmune disorder, characterized by immune-mediated platelet destruction and decreased platelet production. To investigate metabolic alterations associated with paediatric ITP and disease chronicity, we performed untargeted plasma metabolomics analysis in 60 newly diagnosed ITP (nITP) patients, 39 chronic ITP (cITP) patients and 39 healthy controls (HC) from Beijing Children's Hospital between October 2020 and August 2024. A total of 30 differential metabolites were identified between ITP patients and HC, with altered tryptophan metabolism among the most significantly enriched metabolic pathways. Random forest analysis achieved an accuracy of 83.9% and a precision of 95.1%. Glycocholic acid demonstrated strong discriminatory performance, with an area under the receiver operating characteristic curve of 0.882 (95% confidence interval: 0.814-0.950). In addition, phosphatidylcholine-related metabolites and sphingolipid-related metabolites were associated with metabolic alterations observed between nITP and cITP. Overall, paediatric ITP was associated with distinct plasma metabolic alterations, particularly involving tryptophan metabolism, bile acid metabolism and lipid metabolism. These findings provide additional insights into metabolic alterations associated with paediatric ITP and disease chronicity.

Background Large F8 deletions are generally associated with unfavorable immune tolerance induction (ITI) outcomes in children with severe hemophilia A (SHA). Whether intragenic deletion location further stratifies ITI outcomes remains unclear. Objective To evaluate the association between the location of F8 large deletion and ITI outcome in children with SHA and to exploratorily assess residual F8 expression across patients with different deletion locations. Methods This single-center retrospective cohort included 34 children with SHA, F8 large deletions, inhibitors, and evaluable ITI outcomes. Deletions were mapped to FVIII domains and categorized as isolated A1-domain or non-isolated A1-domain deletions. Exploratory F8 mRNA and protein analyses were performed in patients with available blood samples. Results Thirteen patients achieved ITI success or partial success, and 21 experienced ITI failure. Success or partial success was more frequent with isolated A1-domain than non-isolated A1-domain deletions (8/9 vs. 5/25; P < 0.001). Higher historical peak, pre-ITI, and on-ITI peak inhibitor titers were associated with failure in univariate analyses. After multivariable adjustment, isolated A1-domain deletion remained associated with higher odds of success or partial success (adjusted OR, 21.59; 95% CI, 1.24-375.60; P = 0.035). Residual downstream F8 transcripts were detected in the isolated A1-domain subgroup; their biological relevance remains uncertain. Conclusions Intragenic location of F8 large deletions was associated with ITI outcome in this cohort. Isolated A1-domain deletions may identify patients with a more favorable ITI prognosis. Exploratory expression findings require confirmation in larger studies using physiologically relevant models.

Background: Prophylaxis in children with hemophilia B (HB) lacks quantitative approaches that integrate both plasma exposure and tissue distribution. This study aimed to develop and validate a physiologically based pharmacokinetic (PBPK) model of factor IX (FIX) for pediatric HB. The model incorporated the binding of FIX to type IV collagen (Col4) to characterize its distribution in both plasma and extravascular tissues. Methods: A total of 20 children with severe HB were included, contributing 219 plasma samples. The base PBPK model was first established and verified using adult and plasma-derived FIX (pdFIX) data. It was subsequently extrapolated to children by integrating FIX-CTBB parameters and pediatric observations for model calibration. The validated model was used to characterize plasma pharmacokinetics, predict tissue distribution and target attainment, and simulate alternative prophylactic dosing regimens. Results: The model adequately described the plasma pharmacokinetics of FIX in children and predicted substantial extravascular distribution. Total extravascular exposure was approximately sixfold higher than plasma exposure. Marked heterogeneity in target attainment was identified across tissues. Lower target attainment was observed in the colon, pancreas, and brain, whereas delayed attainment occurred in bone and muscle. Simulations of prophylactic dosing regimens suggested that 75 IU/kg twice weekly may provide a favorable balance among sustained FIX exposure, tissue-level target attainment, and treatment burden. Conclusions: This PBPK model provides a mechanistic and quantitative framework for characterizing plasma and tissue exposure to FIX in children with HB and may support individualized optimization of FIX prophylactic dosing.

Background: There is limited evidence directly comparing emicizumab (EMI) prophylaxis and immune tolerance induction (ITI) in children with severe hemophilia A and high-titer inhibitors (SHAcwHTI), particularly bleeding control, quality of life (QoL), and cost. Objectives: This study compared outcomes of EMI vs ITI in SHAcwHTI, focusing on bleeding rates, QoL, and costs. Methods: This single-center retrospective study enrolled SHA children (inhibitor titer ≥5 Bethesda Units/mL), receiving EMI or ITI from January 2020 to December 2024. EMI included loading (initial 4 weeks) and maintenance doses; ITI involved intermediate-dose (factor [F]VIII 100 IU/kg/d) or low-dose (FVIII 50 IU/kg once every other day). Outcomes included annualized bleeding rate (ABR), annualized joint bleeding rate (AJBR), Canadian Hemophilia Outcomes-Kids Life Assessment Tool scores, and medication costs. Results: Among 140 patients (24 in EMI group and 116 in ITI group [40 intermediate-dose ITI and 76 low-dose ITI]), EMI was associated with better bleeding control: median ABR and AJBR were 0 across all observation periods, significantly lower than ITI. For ITI, both ABR and AJBR declined over time but remained higher than those of EMI group. Target joint proportion decreased most markedly in patients receiving EMI (35.7%-0%; P = 0.002). EMI group also showed greater QoL improvement (mean change in parent proxy-reported Canadian Hemophilia Outcomes-Kids Life Assessment Tool scores: +26.6 vs +19.2 vs +19.1; P < .001) and lower medication costs (1993.4 vs 3703.4 vs 3656.3 US$/kg; P < .001). Conclusions: EMI prophylaxis was associated with improved bleeding control and QoL while reduced costs compared with ITI, offering a valuable option for SHAcwHTI, prioritizing immediate hemostasis over the long-term goal of inhibitor eradication, especially in resource-limited settings.

Avatrombopag (AVA), an oral thrombopoietin receptor agonist (TPO-RA), has demonstrated favorable efficacy in the treatment of pediatric immune thrombocytopenia (ITP). However, treatment-related thrombocytosis represents a clinically relevant adverse event that may compromise treatment safety and continuity. Currently, no validated tools are available to predict the risk of AVA-induced thrombocytosis before treatment initiation. In this real-world study, we aimed to develop and validate a predictive model for AVA-associated thrombocytosis in children with ITP. A total of 74 pediatric patients treated with AVA at the Hematology–Oncology Center of Beijing Children’s Hospital between July 2021 and January 2024 were included. We compared the proposed model with established classical machine learning baselines, including Logistic Regression (LR), Support Vector Machine (SVM), Multilayer Perceptron (MLP), Random Forest (RF), and XGBoost, as well as state-of-the-art deep learning models for tabular data, including TabPFN, FT-Transformer, and HyperTab. Among the evaluated models, the FT-Transformer achieved the best performance, with an accuracy of 0.785 ± 0.023 and an area under the receiver operating characteristic curve (AUC) of 0.851 ± 0.021. Model interpretability was enhanced using Shapley Additive Explanations (SHAP), enabling visualization of individual feature contributions to thrombocytosis risk. This AI-driven prediction model, grounded in real-world clinical data, demonstrates robust predictive performance and offers clinically interpretable insights. It provides a reliable reference for individualized risk assessment and supports safer, more precise use of AVA in pediatric ITP management.

Inhibitors are the most severe complication of replacement therapy in patients with hemophilia. Previous studies, along with our clinical observations, have identified distinct incidence rates and clinical manifestations of factor VIII (FVIII) and FIX inhibitors in patients with severe hemophilia A (HA) and HB. To explore different immune responses to FVIII and FIX in patients with HA and HB and elucidate the mechanisms underlying the varying clinical manifestations of these patients, we performed single-cell sequencing on peripheral blood mononuclear cells (PBMCs) collected from 5 patients with HA and 5 with HB with inhibitors. After quality control, a total of 75 051 cells were clustered into 19 subsets. Transcriptome analysis revealed differences in the composition of lymphocyte subsets and the functional status of immune cells between the HA and HB groups. Additionally, immune repertoire analysis indicated variations in the diversity of B- and T-cell clones between the 2 groups. HA group exhibited a relatively higher proportion of B cells and more active B cells, whereas HB group demonstrated a higher proportion of T cells, with more active CD4+ T helper cells. Our study provides insights into the distinct biological processes underlying the distinct immune responses to therapeutic FVIII and FIX in patients with HA and HB, as revealed through single-cell sequencing of PBMCs from patients with hemophilia with inhibitors. The data generated will serve as a valuable resource for future research on how the immune system recognizes and initiates responses to antigens with varying molecular characteristics.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by decreased platelet counts and increased bleeding risk. Although paediatric ITP often resolves spontaneously, some children do not respond to first-line treatments, thus requiring rituximab as a second-line therapy to reduce bleeding risks and corticosteroid exposure. Currently, there is no reliable method to predict the efficacy of rituximab. Our study aimed to develop a machine learning (ML) model to predict the initial response to rituximab in these patients. We analysed data from 156 paediatric ITP patients treated at Beijing Children's Hospital between 2020 and 2023 and identified 25 key predictive features. Among the four evaluated ML models, the multilayer perceptron model exhibited the highest predictive accuracy. SHapley Additive exPlanations analysis revealed that antinuclear antibody titre, thyroglobulin antibody, corticosteroid response and bleeding severity were significant positive predictors, while thyroid peroxidase antibody, CD3+ CD4+ IL-17+ T cells and the duration of disease before rituximab treatment were negatively associated with treatment responses. This ML model could be used to predict rituximab responses in paediatric ITP, which is expected to optimize treatment strategies and improve patient outcomes.

BACKGROUND:Eradication of inhibitors is still a desirable goal for patients with hemophilia A inhibitors. Combining rituximab with immune tolerance induction (ITI) is the secondline regimen, but data and predictors are limited. OBJECTIVES:To evaluate the efficacy of ITI-rituximab and to identify the predictors of prognosis. METHODS:In total, 76 children with high-titer inhibitor prospectively using low-dose ITI together with 1-3 round(s) of rituximab were evaluated for outcomes: success or failure and rapidity (rapid or slow) of inhibitor negativity (ie, inhibitor titers turned negative, inhibitor negativity [IN]). The whole-transcriptome RNA-sequencing (RNA-seq) was used to analyze the gene expression profile of 4 failure patients (excluding F8 large deletion) and 4 rapid success-IN patients. RESULTS:Success IN was achieved in 41 of 76 (53.9%) patients after first-round of rituximab, 50 of 76 (65.8%) after second-round of rituximab, and 51 of 76 (67.1%) after third-round of rituximab. Profile of inhibitor decay followed an exponential decay curve. Time to a given inhibitor titer during ITI-rituximab could be estimated by the model t=ln(Y0-PlateauY-Plateau)k. The newly observed poor prognostic factors included relapse after the first-round of rituximab and early occurence of poor-outcome events. RNA-seq analysis showed 186 upregulated differential expressed genes (DEGs) and 176 downregulated DEGs in failure subjects compared with those in patients with rapid success IN. The upregulated DEGs included CXCL8, NLRP6, CHI3L1, CLEC9A, THBD, and PROS1. The downregulated DEGs included STAT1, TLR7, C1Q, C2, IDO1, and CD38. CONCLUSION:Success IN was achieved in 67% of children with hemophilia A with high-titer inhibitor treated by ITI-rituximab. A model based on the profile of inhibitor-titer decay can be used for predicting outcomes. Humoral immune response and complement and coagulation cascades may act as signals that influence ITI outcomes (ClinicalTrials.gov: NCT03598725).

BACKGROUND:Pediatric patients with autoimmune lymphoproliferative immunodeficiencies (ALPIDs) who exhibit autoimmune cytopenias are frequently diagnosed with immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), or Evans syndrome (ES). These conditions generally necessitate long-term immunosuppressive therapy using medications that are often ineffective and highly toxic before the diagnosis of ALPIDs. A less harmful treatment strategy is needed. METHODS:In this study, we described 23 pediatric patients whose initial symptom was autoimmune cytopenias and who were treated with sirolimus as monotherapy (1.5-4 years) upon being diagnosed with ALPIDs. RESULTS:Children with ALPIDs achieved a sustainable response in immune-related cytopenias and lymphoproliferation manifestations within 3 months of sirolimus monotherapy. The complete response (CR) rate for cytopenias was higher compared to lymphoproliferative manifestations. Thrombocytopenia achieved CR more quickly than anemia and neutropenia. Following sirolimus treatment, there was an increase in the proportion of CD4+CD25+Foxp3+ Tregs and serum TGF-β, while a significant reduction in the DNT ratio was observed. CONCLUSION:Sirolimus resulted in CR and long-lasting responses in most pediatric ALPIDs patients, suggesting it could be considered as a first line for patients requiring prolonged therapy. The increase in Tregs and decrease in DNT after sirolimus treatment may provide insights into the underlying mechanisms of sirolimus in ALPIDs.