摘要
目的:观察第二代酪氨酸激酶抑制剂(TKI)达沙替尼联合化疗并序贯异基因造血干细胞移植(allo-HSCT)治疗Ph染色体阳性急性淋巴细胞白血病(Ph^+ALL)患者的临床疗效、治疗相关副反应及长期生存情况。方法:选取2012年1月至2018年9月于北京大学第一医院确诊为Ph^+ALL,并应用达沙替尼联合化疗及序贯allo-HSCT治疗的19例患者,收集病历资料并进行相关数据统计分析。结果:19例患者中,男性10例,女性9例,中位年龄29(3-48)岁。P190阳性14例,P210阳性5例,3例为复杂染色体核型,3例合并脑膜白血病。化疗方案采用VDCLP方案诱导化疗,缓解后应用HD-MTX及MAE等方案巩固强化治疗。11例(57.9%)诱导化疗开始时即加用达沙替尼,3例(15.8%)因粒缺或感染于诱导缓解后加用,5例(26.3%)由伊马替尼更换为达沙替尼。3例出现副反应,分别表现为皮疹、浮肿、恶心。诱导治疗4周100%患者达形态学缓解;7例(63.6%)达主要分子学缓解(MMR),移植前17例(89.5%)达MMR,15例(78.9%)达完全分子学缓解(CMR)。所有患者均接受亲缘骨髓及外周血造血干细胞移植,中位白细胞及血小板植活时间分别为移植后12、14 d,aGVHD发生率为42.1%,cGVHD发生率为57.9%。移植后,13例患者恢复使用达沙替尼,7例因严重头痛、剧烈呕吐或浆膜腔积液停药,6例持续使用至移植后1年。中位随访42个月(10-72月),3年及5年总生存(OS)率均为94.4%,3年及5年非复发生存(RFS)率分别为81.9%及71.6%。结论:一线选用第二代TKI达沙替尼联合化疗并序贯allo-HSCT治疗Ph^+ALL有效性高,患者临床耐受性良好,患者长期生存可能优于第一代TKI治疗。
Objective:To investigate the clinical efficacy,related side-effectt and long-term survival condition of Philadelphia chromosome positive acute lymphoblastic leukemia(Ph+ALL)patients treated with second generation TKI dasatinib and chemotherapy followed by allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 19 newly diagnosed as Ph^+ALL patients treated by dasatinib,chemotherapy and allo-HSCT from January 2012 to September 2018 were collectd and analyzed.Results:There were 10 males and 9 females with median age of 29 years old.14 patients were BCR/ABL P190 positive while 5 with BCR/ABL P210 positive.Three patients had complex karyotype,and 3 cases were confirmed to have central nervous system leukemia.All the patients received treatment with the induction chemotherapy regimen of VDCLP and consolidation regimens such as HD-MTX and MAE.11 patients(57.9%)received dasatinib during induction chemotherapy,3 patients(15.8%)received dasatinib after remission and 5 patients(26.3%)received dasatinib to replace imatinib.Side-effect appeared in 3 patients including rash,edema and nausea.All the patients got morphological remission and 7 patients(63.6%)got MMR after 4 weeks of induction chemotheraphy.17 patients(89.5%)got MMR and 15 patients(78.9%)got CMR before allo-HSCT.All the patients received related bone marrow and peripheral hematopoietic stem cell transplantation from related donors,the median time of WBC and platelet engraftment were 12 d and 14 d after transplantation,respectively.The incidence rate of aGVHD and cGVHD were 42.1%and 57.9%respectivety.13 patients received therapy of dasatinib after HSCT but 7 patients discontinued because of severe headache,vomiting and serious effusions.All the patients were followed-up for the median time of 42 months,the 3-year and 5-year OS both were 94.4%,and 3-year and 5-year RFS of 81.9%and 71.6%,respectively.Conclusion:First-line administration of dasatinib and chemotherapy followed by allo-HSCT for treatment of Ph^+ALL is effective and patien
作者
李渊
王冰洁
刘微
梁赜隐
尹玥
董玉君
王倩
孙玉华
许蔚林
任汉云
LI Yuan;WANG Bing-Jie;LIU Wei;LIANG Ze-Yin;YIN Yue;DONG Yu-Jun;WANG Qian;SUN Yu-Hua;XU Wei-Lin;REN Han-Yun(Department of Hematology,Peking University First Hospital,Beijing 100034,China)
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2020年第1期18-23,共6页
Journal of Experimental Hematology
基金
北京市自然科学基金(7173271)
中国抗癌协会血液肿瘤专项基金.
