环孢素A联合达那唑±沙利度胺治疗原始细胞不增高骨髓增生异常综合征的疗效及其影响因素分析

Prognostic factors of cyclosporine A combined with danazol with or without thalidomide in myelodysplastic syndrome treatment with low-percentage bone marrow blasts

目的探讨环孢素A(CsA)联合达那唑±沙利度胺治疗原始细胞不增高骨髓增生异常综合征(MDS)疗效及其影响因素。方法收集2011年12月至2019年12月在中国医学科学院血液病医院确诊且接受CsA联合达那唑±沙利度胺治疗的115例原始细胞不增高初诊原发性MDS患者临床资料,回顾性分析其临床特征、疗效及疗效影响因素,并建立疗效预测模型。结果55例(47.8%)患者获得治疗反应,其中11例获得完全缓解,44例获得血液学改善[红系反应率为49.5%(52/105),血小板反应率为40.7%(35/86),中性粒细胞反应率为35.0%(14/40)]。29例红细胞输注依赖的患者中7例(24.1%)脱离输血依赖。总体中位疗效持续时间为20(3~84)个月。单因素分析显示年龄<60岁较≥60岁患者疗效好(52.5%对22.2%,P=0.018),而伴红细胞输注依赖较非红细胞输注依赖患者(24.1%对55.8%,P=0.003)、U2AF1突变型患者较U2AF1野生型患者(26.1%对53.2%,P=0.020)疗效差。多因素分析显示年龄<60岁(OR=4.302,95%CI 1.245~14.820,P=0.021)、无红细胞输注依赖(OR=3.774,95%CI 1.400~10.177,P=0.009)和无U2AF1突变(OR=3.414,95%CI 1.168~9.978,P=0.025)均为获得血液学改善的独立预后因素。联合上述影响疗效的独立预后因素建立疗效预测模型,具有0、1、2、3个危险因素患者的总有效率分别为65%、30%~35%、10%~15%、3%。结论CsA联合达那唑±沙利度胺可有效改善原始细胞不增高MDS患者的血细胞减少症状。年龄<60岁、不伴红细胞输注依赖且无U2AF1突变患者治疗反应较好。

Objective To explore the outcome of cyclosporine A(CsA)combined with danazol with or without thalidomide regimen for myelodysplastic syndrome(MDS)with low-percentage bone marrow blasts and predictive factors for treatment response.Methods Data of 115 subjects who were newly diagnosed with primary MDS with low-percentage bone marrow blasts and were treated with CsA combined with danazol with or without thalidomide from December 2011 to December 2019 in our center were collected.Their clinical features,efficacy,and predictive factors of efficacy were retrospectively analyzed.A model for predicting this response was developed.Results A total of 55 subjects responded(47.8%),including 11 complete responses and 44 hematologic improvements.Fifty-two patients(52/105,49.5%)achieved erythrocyte response;35(35/86,40.7%),platelet response;and 14(14/40,35%),neutrophil response.Of 29 subjects(24.1%),7 who were red blood cell(RBC)transfusion-dependent became independent of transfusion.The median response duration was 20 months(range,3–84 months).In the univariate analysis,patients<0 years had a higher response rate than those≥60 years(52.5%vs 22.2%,P=0.018).Contrarily,the response rate was substantially decreased in patients with RBC transfusion dependence compared with those without RBC transfusion dependence(24.1%vs 55.8%,P=0.003),as well as in patients with the mutated U2AF1 compared with those with the wild-type U2AF1(26.1%vs 53.2%,P=0.020).In multivariable analyses,age<0 years(OR=4.302,95%CI 1.245-14.820,P=0.021),RBC transfusion dependence(OR=3.774,95%CI 1.400–10.177,P=0.009),and U2AF1 mutation(OR=3.414,95%CI 1.168-9.978,P=0.025)were significantly correlated with response.Variables that independently predicted the response were combined to generate the predictive model.According to the model,the overall response rates of patients with 0,1,2,and 3 risk factors were 65%,30%-35%,10%-15%,and 3%,respectively.Conclusion CsA combined with danazol with or without thalidomide regimen could improve cytopenia symptoms in patients with MDS with lowpercentage bone marrow blasts.At age<60 years,no transfusion dependence of RBC and wild-type U2AF1 mutation is a favorable prognostic factor.