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

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.

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

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 infection-related death rate, but extended administration of rhG-CSF did not improve the long-term outcome of refractory SAA and may further facilitate the progression of SAA into MDS/AML.