Effectiveness of sirolimus for early on-set autoimmune cytopenias of autoimmune lymphoproliferative immunodeficiencies.

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.

Analysis of the current situation and influencing factors of home treatment for children with hemophilia in China.

Objective: To investigate the current status of home treatment for children with hemophilia in China and identify key influencing factors.

Methods: Based on a comprehensive literature review and expert consultation, the Questionnaire on Home Treatment for Children with Hemophilia was developed. The study targeted fathers or mothers of children with hemophilia who were registered on the official website of "Home for Hemophilia Patients.

Association of TCRαβ double-negative T cells with the response to glucocorticoids in pediatric patients with immune thrombocytopenia.

Objectives: Pediatric primary immune thrombocytopenia (ITP) is an acquired autoimmune disease that can be partially restored by glucocorticoids. TCRαβCD4CD8 double negative T cells (TCRαβDNT) has been linked to the pathophysiology of ITP; however, the role of TCRαβDNT in response to high-dose dexamethasone (HD-DXM) is unclear. In this study, we aimed to explore the alteration in TCRαβDNT in ITP and the effect of HD-DXM on this subset.

The efficacy, safety, and pharmacokinetics of N8-GP in previously treated Chinese patients with haemophilia A: results from the phase 3b pathfinder10 study.

Introduction: N8-GP (turoctocog alfa pegol) is a recombinant, glycoPEGylated, extended half-life FVIII replacement product approved for treatment of haemophilia A (HA).

Aim: The pathfinder10 (NCT05082116) multicentre, open-label, nonrandomised, single-arm phase 3b trial investigated N8-GP efficacy, safety, and pharmacokinetics in previously treated Chinese patients.

Methods: Patients (≥12 years) with severe HA, FVIII activity <1%, ≥150 exposure days to FVIII products, and no FVIII inhibitors (≥0.

Urine proteomics uncovers biomarker candidates for early identifying rituximab beneficiaries in paediatric steroid-resistant immune thrombocytopenia.

Rituximab (RTX) is an effective treatment for children with steroid-resistant immune thrombocytopenia (ITP), but reliable biomarkers to predict its response early are lacking. We analysed urine samples from 37 steroid-resistant ITP patients-17 RTX responders (RTX-R) and 20 RTX non-responders (RTX-NR)-along with 40 healthy controls using a discovery-validation proteomics workflow. In the discovery cohort, we identified 78 differential proteins (DPs) before treatment and 67 DPs after treatment using the data-independent acquisition (DIA) approach.

Machine learning to forecast rituximab responses for paediatric immune thrombocytopenia: Forging a path towards personalized medical care.

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.

Single-cell sequencing on PBMCs from patients with HA and HB with inhibitors reveals different immune responses to FVIII and FIX.

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.

Outcomes of immune tolerance induction with rituximab to eradicate high-titer inhibitor of hemophilia A: depicted by exponential decay model and the gene expression profile of different outcomes by RNA-sequencing.

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.

Stepwise response-guided treatment protocol superior to thrombopoietin receptor agonist-based second-line therapy for severe persistent/chronic immune thrombocytopenia: a multicenter prospective study from China.

Background: The first second-line international recommendation for children with severe persistent/chronic immune thrombocytopenia is thrombopoietin receptor agonist (TPO-RA)-based treatment; however, <30% can achieve sustained response off-treatment (SRoT), leading to a heavy medical burden.

Objectives: This study aimed to confirm the efficacy of the stepwise response-guided treatment protocol compared with TPO-RA-based second-line therapy for children with severe P/CITP.

Methods: The stepwise response-guided treatment protocol is an individualized stratified immune thrombocytopenia treatment starting with high-dose dexamethasone, then adding rituximab and TPO-RAs in sequential order according to treatment response.

Significant PK variability of plasma-derived FIX concentrates in chinese children with Haemophilia B: A fixed single-dose study of factor IX-CTBB.

Background: The pharmacokinetics (PK) characters of plasma-derived Factor IX (pdFIX) concentrate in Chinese children with Haemophilia B(HB) have not yet been reported.

Aim: To assess the PK parameters of pdFIX in children with severe HB and identify factors that influence FIX PK.

Methods: This non-randomized, open-label PK study enrolled children with severe HB (FIX≤2 %).

A comparison of My Precise Dose and WAPPS-Hemo as dosing tools for optimizing prophylaxis in children with hemophilia A treated with BAY 81-8973.

Background: Dense sampling served as the foundation for the conventional calculation of pharmacokinetic (PK) parameters. Individual PK can now be estimated via sparse sampling thanks to the development of Bayesian population PK (popPK). Both My Precise Dose (MPD) and the Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) use the popPK model of BAY 81-8973 to forecast personalized dosage.

Contrastive Learning With Transformer to Predict the Chronicity of Children With Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is a typically self-limiting and immune-mediated bleeding disorder in children. Approximately 20% of children with ITP experience chronicity, leading to reduced quality of life and increased treatment burden. The accurate prediction of chronicity would enable clinicians to make personalized treatment plans at an early stage.

The impact of Mycoplasma pneumoniae infection on platelets in children with immune thrombocytopenia: a real-world study from China.

Mycoplasma pneumoniae (M. pneumoniae), as one of the susceptible pathogens during childhood, may lead to severe mycoplasmal pneumonia and affect platelet fluctuations. We prospectively collected data on persistent/chronic ITP children who were infected with M.

Differential genes expression of immune tolerance induction in hemophilia A: an exploratory RNA-seq test from a Chinese hemophilia comprehensive care centre.

Background: The production of inhibitors is a serious complication that can arise during coagulation factor replacement therapy for hemophilia A (HA). The primary therapeutic strategy to eliminate inhibitors is immune tolerance induction (ITI), which is known to be an extremely challenging, prolonged, and costly treatment. With the widespread use of RNA sequencing (RNA-seq) to analyze differentially expressed genes (DEGs) across various treatment outcomes, there is potential for predicting ITI outcomes.

Intermediate-dose immune tolerance induction outperforms with faster success, less bleeding, and no added cost in comparison with low dose: a multicenter randomized clinical trial.

Background: Low-dose (LD) or intermediate-dose (MD) immune tolerance induction (ITI) is effective in children with severe hemophilia A (SHA) with high-titer inhibitors (HTIs) and is attractive in countries with economic constraints. However, high-quality evidence of their use is lacking.

Objectives: This was a multicenter randomized clinical trial comparing the efficacy, safety, and medication cost between LD-ITI and MD-ITI for SHA-HTI children.

Therapeutic potential of roxadustat in immune thrombocytopenia: a Mendelian randomization analysis.

Background: Immune thrombocytopenia (ITP) is characterized by immune-mediated platelet destruction and impaired megakaryocyte maturation. Hypoxia-inducible factor-1α (HIF-1α), pivotal in the development of megakaryocytes and immune regulation, is downregulated in ITP. Roxadustat, which stabilizes HIF-1α, has emerged as a potential therapeutic drug for ITP that acts by enhancing HIF-1α-mediated megakaryocyte development and modulating immune responses.

Long-term efficacy and safety of avatrombopag in Chinese children with primary immune thrombocytopenia: A real-world observational study.

Avatrombopag is a newly approved thrombopoietin receptor agonist for second-line treatment of chronic immune thrombocytopenia (ITP) in adults. Our previous study showed its efficacy and safety in a small sample of paediatric ITP patients. However, large samples and long-term data are still lacking.

Real-world use of emicizumab in Chinese children with hemophilia A: Retrospective data from a comprehensive care center.

Importance: Emicizumab (EMI) is efficacious and safe for hemophilia A (HA) prophylaxis. However, its high cost poses a challenge in China.

Objective: To explore the possibility of using reduced-dosage EMI in Chinese HA children.

Case report:Clinical manifestations and therapeutic options following rhTPO-induced neutralizing antibody production in a child with immune thrombocytopenia.

Recombinant human thrombopoietin (rhTPO) is commonly used to improve low platelet status in immune thrombocytopenia (ITP), as one protein product, even with a very low rate, there is still the possibility to produce neutralizing antibodies of thrombopoietin (TPO). We described a 7-year-old boy with ITP and normal TPO levels who had previously received rhTPO for 2 weeks but showed persistent thrombocytopenia and was misdiagnosed as acquired amegakaryocytic thrombocytopenia (AATP) and ineffectively treated with cyclosporine A (CsA) in combination with avatrombopag (AVA). As suspicious the TPO neutralizing antibody development as re-test of TPO level is 0, the CD20 + deletion antibody drug rituximab (RTX) was prescribed and received efficacy.

Development and internal validation of a clinical prediction model for individualized dosing of BAY 81-8973, A full-length recombinant factor VIII, in pediatric patients with haemophilia A.

Background: As the most commonly used coagulation factor VIII (FVIII) concentrate in China, the individualized dosing prediction model of Kovaltry (BAY81-8973) is not fully investigated in pediatric patients. The prophylaxis tailored by population pharmacokinetic (PopPK) model can optimize dosing regimens.

Objectives: This study aimed to develop PopPK models of BAY 81-8973 in pediatric patients, identify quantitative relationships of blood type (as a substitution for von Willebrand factor) on FVIII clearance and provide model-informed precision dosing (MIPD) procedures.

Cost-effectiveness Analysis of Prophylaxis Versus On-demand Treatment for Children With Moderate or Severe Hemophilia A in China.

Background: It is still being determined if prophylaxis (PR) has superior cost effectiveness compared with on-demand (OD) treatment for moderate or severe hemophilia A (HA) children in China.

Objective/purpose: To evaluate the cost-effectiveness of PR and OD treatment for children with moderate or severe HA without inhibitors in China.

Methods: A retrospective cost-effectiveness study was conducted on 640 HA children (373 and 267 children were on the PR and OD treatment, respectively) from January 2021 to November 2022.

Efficacy and safety of recombinant human thrombopoietin for the treatment of chronic primary immune thrombocytopenia in children and adolescents: A multicentre, randomized, double-blind, placebo-controlled phase III trial.

The efficacy and safety of recombinant human thrombopoietin (rhTPO) in children and adolescent patients with chronic primary immune thrombocytopenia (ITP) remains unclear. A multicentre, randomized, double-blind, placebo-controlled phase III trial was performed. Patients aged 6-17 years, diagnosed with ITP and resistant or relapsed to corticosteroid treatment were included.

Exploratory study on the individualized application of eltrombopag in paediatric immune thrombocytopenia guided by therapeutic drug monitoring.

There are variations in individual eltrombopag concentrations that may impact efficacy and adverse drug reactions (ADRs) in paediatric immune thrombocytopenia (ITP). To solve this problem, we tailored the eltrombopag dosage refer to concentration, then followed up to assess concentration value in paediatric ITP. This is a single-centre, prospective, observational study.