强化免疫抑制疗法联合不同方案G-CSF治疗重型再生障碍性贫血患者的长期随访研究  

Treatment of severe aplastic anemia with intensified immunosuppressive therapy and two different regimens with recombinant human granulocyte colony-stimulating factor： a retrospective study based on long-term follow-up

作　　者：李英梅 李星鑫 葛关丽 施均 钱林生 王建祥 郑以州 

机构地区：[1]中国医学科学院、北京协和医学院血液学研究所、血液病医院,天津300020

出　　处：《中华血液学杂志》2010年第7期470-474,共5页Chinese Journal of Hematology

摘　　要：目的 比较强化免疫抑制疗法（IIST）联合两种不同方案重组人粒细胞集落刺激因子（rhG-CSF）治疗重型再生障碍性贫血（SAA）患者的有效性和安全性.方法 回顾性分析1994年3月至2007年12月lIST联合rhG-CSF治疗的176例SAA患者资料.方案A：96例患者IIST后1个月始用rhG-CSF,300μg/次,每周3次、2次、1次各用1个月 方案B：80例患者IIST前始用rhG-CSF 5μg·kg-1·d-1,直至造血功能出现恢复.比较两组的治疗反应、感染相关死亡率和克隆性演变发生率.结果 ①B组患者早期治疗反应率（67.5%）显著高于A组（37.5%）（P〈0.01）,且其获早期治疗反应时间明显提前.B组患者IIST后4个月内感染相关死亡率（6.3%）显著低于A组（16.7%）（P=0.034）.B组患者4年总体生存率[（77.7±4.9）%]显著高于A组[（57.2±5.1）%]（P=0.006）.②IIST后4个月无效的难治性SAA患者,A组者停用rhG-CSF,B组者继续应用,两组12个月疗效、感染相关死亡率及总体生存率差异均无统计学意义（P值分别为0.066、0.296、0.288）,但B组患者转化为骨髓增生异常综合征/急性髓系白血病（MDS/AML）风险显著增高.③多因素分析发现疾病严重程度（RR=1.922,P=0.010）、是否有早期治疗反应（RR=5.749,P〈0.01）为独立预后影响因素,且SAA转化为MDS/AML仅与rhG-CSF疗程相关（RR=1.004,P=0.017）.结论 早期足量应用rhG-CSF联合IIST有助于造血功能恢复,并降低其感染相关死亡率,但延长rhG-CSF疗程并不能进一步提高难治性SAA患者的远期疗效,且增加其转化为MDS/AML的危险性.Objective To compare the efficacy and safety of two different regimens with recombinant human granulocyte colony-stimulating factor （rhG-CSF） combined with intensified immunosuppressive therapy （IIST） in severe aplastic anemia （SAA）. Methods Retrospectively analyzed 176 SAA treated with IIST and rhG-CSF in our hospital from March 1994 to December 2007. Regimen A （Group A, n =96） , rhG-CSF 300 （μg/d was initiated on day 31 after IIST and subcutaneously administered 1-3 days a week for 3 months. Regimen B （Group B, n = 80） , rhG-CSF was initiated at 5μg kg-1 d-1＇ before IIST until hematologic recovery. Results ① The early response rate of Group B （67.5% ） was significantly higher than that of Group A （37.5% ）（P〈0.01） , the interval from IIST to response in Group B was shorter than that in Group A. Moreover, infection-related deaths during first 4 months after IIST were significantly reduced in Group B （6.3% ） when compared with Group A （16. 7% ） （P = 0. 034）. The cumulative incidence of survival at 4 years in Groups B [ （77.7±4.9）% ]was also significantly higher than that in Group A[ （57. 2±5. 1）% ] （P = 0.006）. ② With regard to 93 refractory patients with no response 4 months after IIST, rhG-CSF therapy was continued in Group B meanwhile stopped in Group A. There were no differences between two groups in terms of survival and the response rates （P = 0.288, 0.066）, but there was an increasing risk of evolving into MDS/AML in Group B （22.3%） when compared with Group A （3.71% ） （P=0.023）. ③ By multivari-ate analysis, the severity of disease （P =0. 010,RR = 1. 922） and the early response （P 〈0. 01,RR=5.749） were associated with the overall survival. Moreover, the number of days of rhG-CSF therapy was the only significant risk factor for SAA evolving into MDS/AML （P = 0. 017, RR = 1. 004）. Conclusions The early initiation of rhG-CSF therapy with proper dose might contribute to a desirable early response and reduced inf

关 键 词：贫血 再生障碍性 免疫抑制治疗 粒细胞集落刺激因子 克隆性演变 

分 类 号：R556[医药卫生—血液循环系统疾病]