Treatment of refractory ITP and Evans syndrome by haematopoietic cell transplantation: is it indicated, and for whom? Vaughn J E,Anwer F,Deeg H J Vox sanguinis Several lines of therapy have been established for patients with immune thrombocytopenia (ITP) and Evans syndrome. However, these therapies generally require prolonged administration, lead to profound immunosuppression and increased infectious risk, and are often poorly tolerated. While most patients with these disorders will respond to first-line steroid therapy, others will prove refractory or intolerant to multiple treatments. In these patients (and possibly even selected patients who are not considered refractory), autologous or allogeneic haematopoietic stem cell transplantation (HCT) may provide definitive therapy. We review the literature on the treatment of ITP and Evans syndrome with HCT and discuss its use in the management of these disorders. We also pose, for the purpose of discussion, research questions that will be important to address if HCT is to be considered a viable option for more patients with these diseases. 10.1111/vox.12314

Sirolimus as a rescue therapy in children with immune thrombocytopenia refractory to mycophenolate mofetil. Miano Maurizio,Rotulo Gioacchino Andrea,Palmisani Elena,Giaimo Mariateresa,Fioredda Francesca,Pierri Filomena,Pezzulla Agnese,Licciardello Maria,Terranova Paola,Lanza Tiziana,Cappelli Enrico,Maggiore Rosario,Calvillo Michaela,Micalizzi Concetta,Russo Giovanna,Dufour Carlo American journal of hematology 10.1002/ajh.25119

Sirolimus versus cyclosporine for the treatment of pediatric chronic immune thrombocytopenia: A randomized blinded trial. Mousavi-Hasanzadeh Morteza,Bagheri Bahador,Mehrabi Sarvenaz,Eghbali Aygin,Eghbali Aziz International immunopharmacology INTRODUCTION:Chronic immune thrombocytopenia (ITP) of childhood is still a problem. For treating ITP, several immunosuppressive medications can be considered with various response rates. Our goal was to compare effects of sirolimus and cyclosporine on children with chronic ITP. METHODS:This randomized and blinded trial was carried out on 67 children over 5 years old with chronic ITP. Patients were assigned 1:1 to cyclosporine and sirolimus for 6 months. Platelet count was assessed and compared between 2 study groups at different intervals. The clinical trial registry number was IRCT20180501039499N1. RESULTS:Sixty-one children completed the 6-month treatment. Mean age was 9.3 years with an excess of females. Compared to baseline values, both drugs caused a significant increase in number of platelets over the course of treatment; sirolimus group: 15,800/mcL vs 96,566/mcL, (P < 0.001), cyclosporine group: 14,400/mcL vs 111,266/mcL, P < 0.001,). In addition, differences of platelet number were statistically significant at some treatment intervals (3rd and 6th month, P < 0.05). A quicker response was observed in children receiving cyclosporine. Both drugs had similar rate of response which occurred in 50% of included patients. Finally, sirolimus had a better safety profile. CONCLUSIONS:Our study showed that cyclosporine and sirolimus had an equal rate of response in treating chronic ITP of children. At the same time, the two medications showed significant differences in their side effects. 10.1016/j.intimp.2020.106895

Optimizing the therapeutic window of sirolimus by monitoring blood concentration for the treatment of immune thrombocytopenia. Platelets Previous studies have demonstrated that sirolimus (SRL) is an effective agent for the treatment of refractory/relapsed (R/R) ITP. However, the therapeutic window of sirolimus in the treatment of ITP has not been established. As the toxicity of sirolimus increases with higher blood concentrations, it is crucial to determine the optimal therapeutic concentration of SRL for the treatment of ITP. Thus, in this study, we used a retrospective cohort of ITP patients treated with sirolimus to propose the therapeutic dosage window for sirolimus. A total of 275 laboratory results of SRL blood concentration from 63 ITP patients treated with SRL were analyzed retrospectively. The ITP patients were divided into five groups based on their SRL blood concentration: 0-4 ng/ml, 4-8 ng/ml, 8-12 ng/ml, 12-16 ng/ml and ≥16 ng/ml. In addition to the SRL blood concentration, platelet counts and adverse events that occurred during the first 6 weeks of SRL treatment were analyzed. These findings were then used to establish the decision matrix tables and ROC curves, which helped identify the therapeutic window of SRL. Based on the values and trends of true-positive rate (TPR) and false-positive rate (FPR) in the ROC curve, patients who achieved a SRL blood concentration of 4-12 ng/ml displayed a higher response rate compared to those with a SRL concentration of 0-4 ng/ml or ≥16ng/ml. Additionally, the response rate was better for patients with a SRL concentration of 8-12 ng/ml compared to 4-8 ng/ml. Adverse events were related to the concentration of SRL; however, there was no significant difference in the incidence of adverse events between the concentrations of 4-8 ng/ml and 8-12 ng/ml (> .05). Regression analysis suggested that the concentration of SRL correlated with the patient's age, PLT count at the start of SRL administration, and the dose of SRL. It is suggested that the optimal blood concentration of SRL monotherapy for managing ITP is 8-12 ng/ml. This range may achieve a favorable balance between clinical efficacy and the severity of adverse events. 10.1080/09537104.2023.2277831