地西他滨联合芦可替尼方案治疗初诊慢性粒单核细胞白血病的临床分析  

Clinical analysis of decitabine combined with ruxolitinib regimen in treatment of newly diagnosed chronic myelomonocytic leukemia

作　　者：李佳明 陈玉宝 张苏江 严泽莹 王莹 刘之茵 孙海敏 陈钰 Li Jiaming;Chen Yubao;Zhang Sujiang;Yan Zeying;Wang Ying;Liu Zhiyin;Sun Haimin;Chen Yu(Ruijin Hospital North Affiliated to Shanghai JiaoTong University School of Medicine,Shanghai 201800,China)

机构地区：[1]上海交通大学医学院附属瑞金医院北院血液科,201801

出　　处：《国际输血及血液学杂志》2019年第6期482-487,共6页International Journal of Blood Transfusion and Hematology

基　　金：上海交通大学医学院附属瑞金医院北院院基金(2018ZY03)。

摘　　要：目的 分析地西他滨联合芦可替尼方案治疗初诊慢性粒单核细胞白血病(CMML)患者的临床疗效,并探索相关基因突变对患者疗效及预后的影响.方法 选择2016年3月至2018年8月于上海交通大学附属瑞金医院北院血液科收治的5例初诊为CMML患者为研究对象.其中,男性患者为3例,女性为2例,中位年龄为60岁.本研究治疗方案为地西他滨联合芦可替尼:地西他滨20 mg/(m^2·d),d1~3,芦可替尼5~10 mg/d,d1~28,4周为1个疗程.每个疗程结束后,均对患者骨髓细胞形态学进行复查,以评价疗效,并且观察患者治疗相关不良反应.于治疗前、后分别检测患者骨髓标本中22种急性髓细胞白血病(AML)/骨髓增生异常综合征(MDS)相关基因突变频率(VAF).随访时间截至2019年5月1日,随访间隔为1个月.回顾性分析5例CMML患者的临床特征及疗效,以及治疗前、后患者相关基因VAF的改变.本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求,并且与所有受试者签署临床研究知情同意书.结果 ①5例接受地西他滨联合芦可替尼方案治疗的患者中,3例患者治疗有效,其中患者2获得完全缓解(CR),患者3获得血液学改善(HI),患者5获得骨髓缓解(mCR).患者4治疗无效.患者1疾病进展(PD).全部患者的脾体积较治疗前均有缩小(缩小比例>50%).②5例患者化疗后均出现骨髓抑制,其中患者3骨髓抑制最为严重,骨髓抑制期最长,达2个月;患者1、3和4胸部CT检查结果示肺部感染,经积极抗感染治疗后获得好转;患者1与患者4出现腹泻;患者3出现轻度肝功能损害;患者5出现便秘,经对症支持治疗后均好转.③与治疗前相比,治疗后6个月,患者1骨髓标本中JAK2 V617F VAF(17%下降至0)、SRSF2 P95H VAF(44%下降至39%)降低,CBL H398P VAF(15%上升至60%)、TET2 Q273fs VAF(87%上升至95%)升高;患者2的SRSF2 P95L VAF(69%下降至49%)、CBL R420Q VAF(45%下降至1%)降低,ASXL1 G710fs VAF(47%上�Objective To analyze the clinical efficacy of decitabine combined with ruxolitinib regimen in the treatment of patients with newly diagnosed chronic myelomonocytic leukemia (CMML),and explore the effects of gene mutations on the prediction of efficacy and prognosis.Methods From March 2016 to August 2018, five cases of newly diagnosed patients with CMML admitted to the Department of Hematology,Ruijin Hospital North Affiliated to Shanghai JiaoTong University School of Medicine were selected as study subj ects.Among them,there were 3 male patients and 2 female patients,with a median age of 60 years.In this study,the treatment regimens were deccitabine combined with rucotinib:deccitabine 20 mg/(m^2 ·d),d1~3;rucotinib 5~10 mg/d,d1~28,4 weeks as a course of treatment.At the end of each treatment course,the efficacy was evaluated based on the bone marrow cell morphology of the patients. Adverse reactions related to treatment were observed.The variant allele frequency (VAF)of 22 types of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS)related genes was detected before and after treatment.The follow-up period was up to May 1,2019,with an interval of 1 month.The clinical features and efficacy of 5 patients with CMML were retrospectively analyzed,as well as the changes of related VAF of genes before and after treatment.The procedure of this study is accordance with the requirement of the revised World Medical Association Declaration of Helsinki in 2013.Consent form was obtained from all subj ects.Results ① Among the 5 patients received the combination of descitabine and rucotinib regimen,3 patients obtained overall response,among which patient 2 received complete remission (CR),patient 3 received hematologic improvement (HI),and patient 5 received bone marrow complete remission (mCR).Patient 4 had no effect.Patient 1 had disease progression (PD).All patients'spleen size decreased (extent of reduction>50%).② All the 5 patients showed myelosuppression after chemotherapy, among which patient 3 had the most seve

关 键 词：白血病 粒-单核细胞 慢性 突变 治疗结果 地西他滨 芦可替尼 

分 类 号：R73[医药卫生—肿瘤]