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.

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.

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.

Spatial Transcriptomics Unveils the Blueprint of Mammalian Lung Development.

Mammalian lung development is a complex, highly orchestrated process involving the precise coordination of diverse cell types. Despite significant advances, the spatial gene expression patterns and regulatory mechanisms within the developmental niches of different lung structures remain incompletely understood. In this study, we present a comprehensive spatial transcriptomic atlas of mouse lung development, spanning from the early pseudoglandular to the alveolar stage.

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.

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.

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.

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.

A long term outcomes analysis of severe haemophilia A boys receiving 4 years prophylaxis on the Chinese Haemophilia Individualized escalating low dose Prophylaxis (CHIPS).

Background: The Chinese Haemophilia Individualized Prophylaxis Study (CHIPS), which was launched in 2016, reported a significant reduction in haemarthrosis over a one-year study. However, its long-term efficacy requires verification. This paper summarizes the clinical outcomes of 18 severe haemophilia A (SHA) patients who completed one year on the CHIPS and 3 more years of follow-up.

Low-dose immune tolerance induction for severe hemophilia A inhibitor patients: Immunosuppressants are generally not necessary for inhibitor-titer below 200 BU/mL.

Importance: It remained unclear that the efficacy comparison between low-dose immune tolerance induction (LD-ITI) incorporating immunosuppressants (IS) when severe hemophilia A (SHA) patients had inhibitor-titer ≥200 Bethesda Units (BU)/mL (LD-ITI-IS regimen) and LD-ITI combining with IS when SHA patients had inhibitor-titer ≥40 BU/mL (LD-ITI-IS regimen).

Objective: To compare the efficacy of the LD-ITI-IS regimen with that of the LD-ITI-IS regimen for SHA patients with high-titer inhibitors.

Methods: A prospective cohort study on patients receiving LD-ITI-IS compared to those receiving LD-ITI-IS from January 2021 to December 2023.

The Differences of Serum Thrombopoietin Levels Between Acquired Aplastic Anemia and Immune Thrombocytopenia in Pediatric Patients.

Thrombopoietin (TPO) is the critical regulator of platelet production. However, the role of TPO in pediatric patients with thrombocytopenic disorders has not been fully elucidated. In the present study, we attempted to investigate serum TPO levels in patients with acquired aplastic anemia (aAA) and immune thrombocytopenia (ITP).

The early and rapid response to daratumumab in children with chronic refractory immune thrombocytopenia from a referral single centre of China.

Chronic refractory primary immune thrombocytopenia (CRITP) is currently defined as refractory to multiple therapeutic of second-line agents with or without splenectomy, faced with the threat of severe bleeding and challenging to obtain effective treatment. Although stable and effective drug therapy is needed, it is tough to find one. Daratumumab (Dara), an anti-CD38 monoclonal antibody presented the target cloned plasma cells in multiple myeloma, has also been reported to be effective in refractory autoimmune cytopenia in some case or series reports and ongoing clinical trials for adult patients with CRITP.