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Congenital myelofibrosis (cMF) is a rare inherited bone marrow failure disorder. We report a 26-year-old Chinese male with a 24-year history of recurrent epistaxis and thrombocytopenia. Laboratory findings revealed severe thrombocytopenia (18 × 10⁹/L) and bone marrow biopsy showed MF-3 fibrosis with impaired megakaryopoiesis. Genetic analysis identified a novel homozygous nonsense mutation in MPIG6B (c.420T > A, p.Y140X), leading to a diagnosis of cMF. This case expands the clinical spectrum of MPIG6B-related disorders and illustrates the long-term natural history in a non-consanguineous population. The patient achieved clinical stability with eltrombopag and danazol.

Mesenchymal stem cells (MSCs) possess potent immunomodulatory activity and have been extensively investigated for their therapeutic potential in treating inflammatory disorders. However, the mechanisms underlying the immunosuppressive function of MSCs are not fully understood, hindering the development of standardized MSC-based therapies for clinical use. In this study, we profile the single-cell transcriptomes of MSCs isolated from adipose tissue (AD), bone marrow (BM), placental chorionic membrane (PM), and umbilical cord (UC). Our results demonstrate that MSCs undergo a progressive aging process and that the cellular senescence state influences their immunosuppressive activity by downregulating PD-L1 expression. Through integrated analysis of single-cell transcriptomic and proteomic data, we identify GATA2 as a regulator of MSC senescence and PD-L1 expression. Overall, our findings highlight the roles of cell aging and PD-L1 expression in modulating the immunosuppressive efficacy of MSCs and implicating perinatal MSC therapy for clinical applications in inflammatory disorders. Mesenchymal stem cells (MSC) are used for immunosuppressive therapy and a uniform source or heterogeneity characterisation is needed. Here the authors use multi-omics to compare human MSC from different sources and ages of donors and show differences in gene expression and immunosuppressive function.

Interferon therapy has been used in clinical practice for more than three decades to treat polycythemia vera (PV) and essential thrombocythemia (ET). However, there has been no systematic investigation of its expected outcomes and potential risks. We performed a systematic review and single-arm meta-analysis to assess the clinical outcomes (hematological response, molecular response, vascular events, hematological transformation, and adverse events) after interferon therapy for patients with PV and ET. A systematic search identified 37 reports, including data from 1794 patients that were published before March 2021. The pooled overall hematological response (OHR) rate was 86%, with better OHR rates observed in studies using long-acting interferon (p < 0.001) and studies with younger patients (p = 0.038). The pooled overall molecular response rate was 48%, and inter-study heterogeneity was also related to patient age (p = 0.009). The overall incidence was 0.42/100 person-years for thrombosis, 0.01/100 person-years for hemorrhage, 0.21/100 person-years for myelofibrotic transformation, and 0.08/100 person-years for leukemic transformation. Compared with hydroxyurea, interferon produced a non-inferior hematological response and a superior molecular response. In conclusion, interferon therapy provided high rates of hematological and molecular response for patients with PV and ET and was associated with a favorable prognosis.

Objective This study’s objective was to develop an algorithm that mapping the Haem-A-QoL scores to EQ-5D-5L utility scores in patients with hemophilia in China. Methods A national sample of 862 patients with hemophilia completed both the EQ-5D-5L and Haem-A-QoL instruments. Eight regression models were selected to develop the mapping algorithm, they were: the ordinary least squares, general linear regression, Tobit regression, censored least absolute deviation, mixture beta regression, adjusted limited dependent variable mixture, the two-part, and robust MM-estimator model. Root mean squared error (RMSE), mean absolute error (MAE), and R-square ( R 2 ) calculated using the tenfold cross-validation and random sample validation methods were used to assess the predictive ability of the models. Results Based on RMSE, MAE, and R 2 , the mixture beta regression model with selected Haem-A-QoL subscale scores as the predicted variables showed the best performance. Conclusions Our mapping algorithm bolsters the calculation of QALYs while conducting an economic evaluation of hemophilia-related interventions when only Haem-A-QoL data are available. The external validity of the algorithm should be further assessed in the other populations.

Von Willebrand disease (VWD) is an inherited bleeding disorder resulting from a deficiency in von Willebrand factor (VWF), either quantitative or qualitative. Recombinant VWF (rVWF) presents a novel therapeutic option for patients with VWD. Produced in Chinese hamster ovary cells, rVWF is free of animal or human plasma proteins, thus eliminating the risk of pathogen transmission. It preserves the full range of VWF multimers, including ultra-large multimers, which are essential for hemostasis. Research indicates that rVWF demonstrates superior pharmacokinetics and pharmacodynamics compared to plasma-derived VWF, offering a longer terminal half-life, enhanced platelet adhesion and aggregation, and more robust factor VIII stabilization. These properties contribute to rVWF’s increased hemostatic efficacy in managing bleeding episodes and perioperative surgical bleeding in adults and children with VWD, as well as the routine prophylaxis for adults to reduce the frequency of bleeding episodes. Furthermore, rVWF is well-tolerated with a low thrombotic risk, making it a promising treatment option and addressing a significant clinical need globally.

AbstractObjectiveTo assess the efficacy and safety of CM313, an anti-CD38 monoclonal antibody, in adults with persistent or chronic primary immune thrombocytopenia.DesignMulticentre, randomised, placebo controlled, phase 2 trial.SettingFive hospitals in China, 16 January to 11 June 2024.Participants45 patients aged ≥18 years with persistent or chronic immune thrombocytopenia who failed to respond to, or relapsed after, glucocorticoid treatment but had previously responded to standard first line treatment.InterventionsPatients were randomised to receive intravenous CM313 (16 mg/kg) or placebo weekly for eight weeks.Main outcome measuresThe primary outcome was overall response rate (at least two consecutive platelet counts ≥30×109/L, a minimum doubling from baseline, and no bleeding) at week 8. A secondary outcome was time to the first two consecutive platelet counts ≥50×109/L.ResultsOf 56 patients screened, 45 were randomised to receive CM313 (n=30) or placebo (n=15). At week 8, the overall response rate was higher in the CM313 group (83%; 25/30) compared with placebo group (20%; 3/15): difference 63.3% (95% confidence interval 33.7% to 81.3%; P<0.001). The median time to a platelet count of ≥50×109/L was one week in the CM313 group but was not reached in the placebo group (P<0.001). The median cumulative response duration for platelet counts ≥50×109/L was 18 weeks in the CM313 group versus three weeks in the placebo group (P=0.004). Treatment emergent adverse events occurred in 87% (26/30) of patients in the CM313 group and 80% (12/15) in the placebo group, with infusion related reactions and petechiae being the most common.ConclusionCM313 showed a favourable safety profile and encouraging efficacy in adults with persistent or chronic primary immune thrombocytopenia, characterised by rapid increase in platelet count, sustained platelet responses, and manageable adverse events.Trial registrationClinicalTrials.gov NCT06199089.

Objective The aim of this study was to evaluate the psychometric properties of the EQ-5D-5L and SF-6D, and to compare their performance among patients living with haemophilia in China. Methods A total of 875 Chinese patients completed the EQ-5D-5L, SF-6D, and Haem-A-QoL questionnaires. Construct validity of the EQ-5D-5L and SF-6D dimensions and indices was assessed by testing hypotheses relating these measures to Haem-A-QoL and clinical measures. The Spearman correlation coefficient was used to assess convergent validity, and oneway analysis of variance (F statistic) was used to assess the known-groups validity (discriminatory power). The agreement between EQ-5D-5L and SF-6D indices was assessed using the intraclass correlation coefficient (ICC) and the Bland-Altman plot. Results Both the EQ-5D-5L and SF-6D indices showed acceptable ceiling and floor effects. As hypothesised, both EQ-5D-5L and SF-6D were significantly correlated with Haem-A-QoL (both dimensions and overall score). EQ-5D-5L and SF-6D indices as well as EQ-VAS differentiated patients are known to differ in severity of haemophilia, bleeding status, disabling levels, and comorbidity. The F statistics in the known-groups comparisons suggested that the EQ-5D-5L was slightly more discriminative than the SF-6D. ICC (0.41) and Bland-Altman plot confirmed that the agreement between the EQ-5D-5L and SF-6D indices was poor. Conclusion Both EQ-5D-5L and SF-6D showed satisfactory construct validity in the measurement of the HRQoL among patients with haemophilia. However, the two instruments may not be used interchangeably in this patient population due to their poor agreement and differing discriminatory power.

Background Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients. Methods Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 10 9 /L) after 8 weeks of treatment. Results The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83–68.63; p  < 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39–86.87; p  < 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment. Conclusions In ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile. Trial registration Clinical trials.gov NCT03222843 , registered July 19, 2017, retrospectively registered.