利妥昔单抗治疗异基因造血干细胞移植后EB病毒病的疗效和安全性

 目的 了解利妥昔单抗治疗异基因造血干细胞移植（allo-HSCT）后EB病毒（EBV）病的疗效和安全性。方法 回顾性分析2006年6月—2012年3月在北京大学人民医院诊断为allo-HSCT后EBV病并应用利妥昔单抗治疗的26例患者，其中临床诊断EBV病15例，活检确诊（移植后淋巴组织增殖性疾病，PTLD）11例。利妥昔单抗静脉输注375 mg/m²，每周1次。采用非霍奇金淋巴瘤（NHL）的疗效标准判定疗效，采用通用的毒性分级标准判定输注过程中的不良反应。结果共应用利妥昔单抗78例次，中位3（1~6）例次。利妥昔单抗输注过程中无严重不良反应发生。治疗后1、2、3、4、8周的累积完全缓解（CR）率分别为（11.5±6.3）%、（42.2±10.2）%、（64.4±10.0）%、（74.6±9.4）%、（87.3±7.9）%。总有效率84.6%，CR率73.1%；单个器官受累患者的CR率高于多器官受累患者（10/10比9/16，P=0.023），临床诊断的EBV病患者CR率高于PTLD患者(13/15比6/11，P=0.095），但差异无统计学意义。自首剂利妥昔单抗应用后的1年和2年总生存（OS）率分别为（55.7±10.2）%和（39.6±12.4）%。单器官受累患者的存活率高于多器官受累患者（8/10比5/16，P=0.041），临床诊断的患者存活多于PTLD患者(11/15比2/11，P=0.015）。结论 利妥昔单抗治疗EBV病安全有效，建议根据临床诊断在单器官受累时即开始治疗，同时争取尽早获取病理结果。利妥昔单抗的治疗方案需要前瞻性研究提供循证医学的证据来进一步规范。

The efficacy and safety of rituximab in treatment of Epstein-Barr virus disease post allogeneic hematopoietic stem-cell transplantation

Objective To investigate the efficacy and safety of rituximab on Epstein-Barr virus (EBV) disease post allogeneic hematopoietic stem-cell transplantation.Methods A retrospective analysis was performed based on clinical data of 26 patients diagnosed as EBV disease and received rituximab from June 2006 to March 2012 in People′s Hospital, Beijing University. Eleven patients were diagnosed as posttransplant lymphoproliferative disorders (PTLD) by histopathology and remaining 15 were diagnosed as probable EBV disease. Patients received a rituximab dose of 375 mg/m² once a week. Efficacy was evaluated as revised response criteria for non-hodgkin lymphoma (NHL), and side effects during infusion were evaluated by Common Terminology Criteria for Adverse Events.Results Patients received 78 infusions with a median of 3(1-6) infusions in each. There were no severe side effects during the infusion of rituximab. The 1^st, 2^nd, 3^rd, 4^th, 8^th week cumulative complete remission (CR) were (11.5±6.3)%, (42.2±10.2)%, (64.4±10.0)%, (74.6±9.4)%, (87.3±7.9)%, respectively. The overall response rate was 84.5%, and the CR rate was 73.1%. The CR rate was higher among patients with single organ involved than those with multiple organs involved (10/10 vs 9/16, P=0.023). The CR rate was higher in patients with probable EBV disease than those with PTLD (13/15 vs 6/11，P=0.095), while there was no statistically significant difference. The incidence of one-year and two-year overall survival since onset of rituximab were (55.7±10.2)% and (39.6±12.4)%, respectively. Survival rate was higher among the patients with single organ involved than those with multiple organ involved (8/10 vs 5/16, P=0.041). Survival rate was higher in patients with probable EBV disease than those with PTLD(11/15 vs 2/11, P=0.015).Conclusions Rituximab appears to be safe and effective for EBV disease. Due to a potential good response in probable EBV disease, we suggest rituxmab should be given based on probable EBV disease; meanwhile the pathological results should get early if possible. Prospective trial is needed to provide evidence so as to define optimal therapy of rituxmab.