Sex-specific impact on disease outcome and the mutational landscape in essential thrombocythemia:A retrospective cohort study

To the Editor:Male sex has been confirmed to be an independent risk factor for survival in patients with essential thrombocythemia(ET).[1,2]Sexual dimorphism significantly contributes to patient heterogeneity,and adopting a sex-informed perspective has emerged as a pioneering paradigm in the field of precision medicine.Investigating the spectrum of sex disparities among patients diagnosed with ET holds substantial scientific justification.Furthermore,sex influences the presentation,disease phenotypes,symptom expression,and clinical outcomes of classical Philadelphia chromosome-negative myeloproliferative neoplasm(MPN).[3,4]The objective of our study was to comprehensively elucidate the impact of sex on ET by exploring disease genotype and phenotype as well as clinical outcomes.

Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia:a prospective,single arm,phase I trial

Patients with refractory immune thrombocytopenia(ITP)frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing therapies.Umbilical cord-derived mesenchymal stem cells(UC-MSCs)present a promising alternative,capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune disorders.This prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory ITP.The research design included administering UC-MSCs at escalating doses of 0.5×10^(6)cells/kg,1.0×10^(6)cells/kg,and 2.0×10^(6)cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase,followed by a dose of 2.0×10^(6)cells/kg weekly for the dose-expansion phase.Adverse events,platelet counts,and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up period.Ultimately,12(with an addition of three patients in the 2.0×10^(6)cells/kg group due to dose-limiting toxicity)and six patients were enrolled in the dose-escalation and dose-expansion phase,respectively.Thirteen patients(13/18,72.2%)experienced one or more treatment emergent adverse events.Serious adverse events occurred in four patients(4/18,22.2%),including gastrointestinal hemorrhage(2/4),profuse menstruation(1/4),and acute myocardial infarction(1/4).The response rates were 41.7%in the dose-escalation phase(5/12,two received 1.0×10^(6)cells/kg per week,and three received 2.0×10^(6)cells/kg per week)and 50.0%(3/6)in the dose-expansion phase.The overall response rate was 44.4%(8/18)among all enrolled patients.To sum up,UC-MSCs are effective and well tolerated in treating refractory ITP(ClinicalTrials.gov ID:NCT04014166).

Chinese expert consensus on the management of chimeric antigen receptor T cell therapy-associated coagulopathy

Chimeric antigen receptor T-cell(CAR-T)therapy has greatly improved the disease remission rate and long-term survival rate of patients with relapsed/refractory hematological malignancies.[1-3]Currently,several commercial CAR-T products are available in the market and numerous CAR-T clinical trials have been conducted.Attention should be paid to the safety of CAR-T therapy.The main adverse effects of CAR-T therapy are cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS).[4]