芦可替尼联合泼尼松、沙利度胺和达那唑治疗骨髓纤维化的探索性研究  

Ruxolitinib combined with prednisone,thalidomide and danazol for treatment of myelofibrosis:a pilot study

作　　者：徐泽锋 秦铁军 张宏丽 方力维 潘丽娟 胡耐博 曲士强 李冰 肖志坚 Xu Zefeng;Qin Tiejun;Zhang Hongli;Fang Liwei;Pan Lijuan;Hu Naibo;Qu Shiqiang;Li Bing;Xiao Zhijian(Institute of Hematology and Blood Diseases Hospital,CAMS & PUMC,The State Key Laboratory of Experimental Hematology,Tianjin 300020,China)

机构地区：[1]中国医学科学院、北京协和医学院血液病医院(血液学研究所),实验血液学国家重点实验室,天津300020

出　　处：《中华血液学杂志》2019年第1期24-28,共5页Chinese Journal of Hematology

基　　金：国家自然科学基金(81530008、81600098、81770129);天津市科技计划(15ZXLCSY00010);中国医学科学院医学与健康科技创新工程(2016-I2M-1-001);协和学者与创新团队发展计划.

摘　　要：目的探讨芦可替尼(RUX)联合PTD方案(泼尼松+沙利度胺+达那唑)治疗骨髓纤维化(MF)的疗效和安全性。方法对符合2016年WHO的MF诊断标准的MF患者,采用芦可替尼(RUX)联合PTD方案治疗,并评价该方案的临床疗效、血细胞计数变化和不良反应。结果7例MF患者纳入研究,其中原发性骨髓纤维化(PMF)6例,原发性血小板增多症后骨髓纤维化(post-ET MF)1例;JAK2V617F突变4例,CARL突变1例,MPLW515突变1例,以上3种始动基因突变均阴性1例。7例患者治疗前均有肋缘下可触及的脾肿大。7例患者中5例获得临床改善,2例疾病稳定。7例患者均有不同程度的临床症状改善,6例患者有不同程度的脾脏缩小。3例患者接受芦可替尼单药治疗,均出现不同程度的血红蛋白浓度和血小板计数下降,改用芦可替尼联合PTD方案后血红蛋白浓度和血小板计数均明显上升。所有7例接受芦可替尼联合PTD方案治疗患者的血红蛋白浓度中位上升值为30(18~54)g/L,血小板计数中位上升值为116(13~369)×10^9/L,其中3例患者因血小板计数明显上升而调高芦可替尼剂量。全部7例患者均未发生血液学不良反应,未发生Ⅲ/Ⅳ级非血液学不良反应,Ⅰ/Ⅱ级非血液学不良反应包括便秘、腹胀、下肢水肿、丙氨酸转氨酶升高和齿龈感染各1例。结论芦可替尼联合泼尼松、沙利度胺和达那唑治疗MF患者,可减少芦可替尼的血液学不良反应,使血红蛋白和血小板计数上升、提高临床疗效,且安全性好。Objective To evaluate the efficacy and tolerability of ruxolitinib combined with prednisone,thalidomide and danazol for treatment of in myelofibrosis (MF).Methods Patients of MF according to the WHO 2016 criteria,received ruxolitinib (RUX) combined with prednisone,thalidomide and danazol (PTD).The response,changes of blood counts and adverse events were evaluated.Results Six PMF and one post-ET MF patients were enrolled.Four patients presented JAK2V617F mutation,one CALR mutation,one MPL mutation,one triple-negative.Responses per IWG-MRT criteria were clinical improvement in 5 patients,stable disease in 2 ones,spleen response in 6 ones.All of 7 patients were symptomatic responses,four patients achieved at least 50% improvement from baseline on MPN-SAF TSS.Three patients initially treated with RUX alone,all of 3 patients experienced treatment-associated anemia and thrombocytopenia.Then these 3 patients received RUX combined with PTD,both hemoglobin and platelet increased significantly.Four patients initially treated with RUX combined with PTD.Increased levels of hemoglobin and platelet were seen in all of 7 patients received RUX combined with PTD with maximum increased hemoglobin of 30(18-54) g/L and maximum increased platelets of 116(13-369)×10^9/L,respectively from baseline.The treatment dose of RUX increased due to improved platelet count in 3 patients.The frequent non-hematologic adverse events grade 1-2 were constipation,abdominal distension,crura edema and increased ALT.Conclusions RUX combined with PTD for treatment of MF may modulate initial hematologic toxicity observed when RUX alone,and may increase response due to improved levels of hemoglobin or platelet.

关 键 词：原发性骨髓纤维化 芦可替尼 泼尼松 沙利度胺 达那唑 

分 类 号：R551.3[医药卫生—血液循环系统疾病]