干扰素α联合沙利度胺治疗JAK2V617F基因突变阳性Bcr/Abl阴性骨髓增殖性肿瘤的临床疗效研究

Therapeutic Effect of Interferonb Alpha Combined with Thalidomide on JAK2V617F Mutation-positive and Bcr/Ablnegative Patients with Myeloproliferative Neoplasm

目的研究干扰素α(IFN-α)联合沙利度胺治疗JAK2V617F基因突变阳性Bcr/Abl阴性骨髓增殖性肿瘤(MPN)的临床疗效。方法选取2006—2016年哈励逊国际和平医院血液科门诊及住院部收治的符合纳入标准的Bcr/Abl阴性MPN患者150例,其中JAK2V617F基因突变阳性者共122例,包括真性红细胞增多症(PV)56例,原发性血小板增多症(ET)66例。根据药物治疗反应将JAK2V617F基因突变阳性患者分治疗组1[57例,给予IFN-α联合沙利度胺维持治疗,其中PV患者25例(A1亚组),ET患者32例(B1亚组)];治疗组2[35例,给予羟基脲联合沙利度胺维持治疗,其中PV患者15例(A2亚组),ET患者20例(B2亚组)];对照组[30例,给予羟基脲维持治疗,其中PV患者16例(A3亚组),ET患者14例(B3亚组)]。记录患者的临床缓解率,治疗前、治疗后半年、治疗后1年JAK2V617F基因突变比例,骨髓细胞形态学、骨髓病理学检查结果,无疾病进展生存情况和药物不良反应。结果 A1、A2、A3亚组临床缓解率比较,差异无统计学意义(P>0.05)。B1亚组临床缓解率高于B3亚组(P<0.05)。治疗方法、时间在JAK2V617F基因突变比例上存在交互作用(P<0.05),治疗方法、时间在JAK2V617F基因突变比例上主效应显著(P<0.05);治疗后半年、1年A1亚组JAK2V617F基因突变比例低于A2、A3亚组,B1亚组JAK2V617F基因突变比例低于B2、B3亚组(P<0.05);治疗组1、治疗组2、对照组无疾病进展生存率分别为91.2%(52/57)、80.0%(28/35)、60.0%(18/30)。药物不良反应在3组之间相似,患者均能耐受。结论IFN-α联合沙利度胺治疗JAK2V617F基因突变阳性Bcr/Abl阴性MPN能提高临床缓解率和无疾病进展生存率,并且其可降低JAK2V617F基因突变比例。

Objective To investigate the therapeutic effect of interferon alpha(IFN-α)combined with thalidomide in myeloproliferative neoplasm(MPN)patients who are Bcr/Abl-negative and JAK2V617F mutation-positive.Methods According to the inclusion criteria,we enrolled 150 Bcr/Abl-negative MPN hematology outpatients and inpatients treated in Harrison International Peace Hospital from 2006-2016.PCR screening selected 122 patients presenting the JAK2V617F mutation-positive,including 56 polycythemia vera(PV)patients and 66 essential thrombocytosis(ET)patients.According to the tolerance-based therapy,the patients were categorized into 3 groups:group 1〔IFN-αplus thalidomide,n=57,including subgroup A1(PV,n=25)and subgroup B1(ET,n=32)〕,group 2〔hydroxyurea plus thalidomide,n=35,including subgroup A2(PV,n=15)and subgroup B2(ET,n=20)〕,as well as control group〔hydroxyurea,n=30,including subgroup A3(PV,n=16)and subgroup B3(ET,n=14)〕.Clinical remission rate,before treatment,6-month,1-year after treatment JAK2V617F mutation ratio status,morphologic and pathologic features of bone marrow,the disease progression and survival and adverse reaction were recorded.Results There was no significant difference in the clinical remission rate of subgroup A1,subgroup A2 and A3(P>0.05).The clinical remission rate was higher in subgroup B1 compared to B3(P<0.05).Significant interaction and main effects on JAK2V617F mutation were observed between treatment regimen and duration of treatment(P<0.05).In response to 6-month,1-year after treatment,JAK2V617F mutation was reduced in subgroup A1 compared to A2 or A3(P<0.05),and decreased in subgroup B1 compared to B2 or B3(P<0.05).The disease-free survival rates in 3 groups were 91.2%(52/57),80.0%(28/35)and 60.0%(18/30),respectively.Adverse drug reaction rates were low and showed no significant differences between 3 groups.Conclusion The therapeutic responses of JAK2V617F mutationpositive and Bcr/Abl-negative MPN patients to the combination treatment of INF-αand thalidomide can improve the clinical remission rate and disease-free survival rates,and it can reduce JAK2V617F mutation ratio.