芦可替尼对慢性移植物抗宿主病患者的疗效及安全性研究

Clinical efficacy and safety of ruxolitinib in treatment of chronic graft versus host disease

目的观察芦可替尼治疗慢性移植物抗宿主病(chronic graft versus host disease,cGVHD)的临床效果,并探讨其安全性。方法收集2017年7月1日至2019年2月1日解放军联勤保障部队第920医院42例cGVHD患者的临床资料,芦可替尼治疗方案分为两种:①当cGVHD患者受累器官为皮肤、口腔、眼睛、关节、生殖道时,在原有免疫抑制剂治疗基础上加用芦可替尼5 mg/d(当患者体质量≤25 kg或当芦可替尼与强效CYP3A4抑制剂或者氟康唑合并给药时总剂量减半);②当cGVHD患者受累器官为肺部、肝脏、胃肠道等,予芦可替尼5 mg/d+甲泼尼龙1 mg·kg^-1·d^-1治疗。分别于cGVHD患者使用芦可替尼治疗后1、3个月评估患者疗效。同时每周检测患者外周血象、凝血功能、人巨细胞病毒拷贝数及胸部CT。结果42例cGVHD患者使用芦可替尼治疗后1、3个月总体反应疗效评估ORR分别为85.7%(36/42)、95.2%(40/42)。治疗过程中有6例患者出现肺部感染;有4例患者出现出血事件;有12例患者出现人巨细胞病毒感染或病毒拷贝数持续上升;有8例患者出现明显骨髓抑制,均为Ⅰ~Ⅱ级。中位随访时间为4(1~19)个月,无患者失访,随访期间有4例(9.5%,4/42)患者死亡,其死亡原因包括白血病复发、肺部感染及cGVHD病情控制不佳。结论芦可替尼治疗慢性移植物抗宿主病效果显著,不良反应低,可预防、可耐受。

ObjectiveTo study the clinical efficacy and safety of ruxolitinib in the treatment of chronic graft versus host disease(cGVHD).MethodsWe collected the clinical data of 42 cGVHD patients after receiving allogeneic hematopoietic stem cell transplantation from July 1,2016 to February 1,2019 in our hospital.There were 2 specific treatment regimens.For the patients diagnosed with the skin,mouth,eyes,joints or genital tract involvement,5 mg/d ruxolitinib was given(when the patient weighs less than 25 kg,or ruxolitinib is administered in combination with a potent CYP3A4 inhibitor or fluconazole,the total dose is halved)on the basis of the original immunosuppressant therapy.For those diagnosed with lung,liver or gastrointestinal tract involvement,5 mg/d ruxolitinib and 1 mg/(kg·d)methylprednisolone were given on the basis of the original immunosuppressant therapy.The clinical efficacy was evaluated in 1 and 3 month after treatment.Peripheral blood test,coagulation function,copy number of human cytomegalovirus and chest CT scanning were performed every week.ResultsAmong the 42 cGVHD patients,overall response rates(ORR)were 85.7%(36/42)and 95.2%(40/42)at 1 month and 3 months after treatment,respectively.In the process of this study,6 patients developed pulmonary infection,and 4 patients experienced bleeding events.There were 12 patients having human cytomegalovirus and epstein-barr virus infection or the virus copy number being continued to rise.Bone marrow suppression at grade ofⅠ~Ⅱpresented in 8 patients.During the follow-up period of 4(1~19)months,no one patient was lost,and 4 patients(9.5%,4/42)died,due to leukemia recurrence,pulmonary infection and poor control of cGVHD.ConclusionRuxolitinib has significant efficacy in the treatment of cGVHD,with low adverse reactions and preventable and tolerable effects.