G-CSF治疗后中性粒细胞反应预测重型再生障碍性贫血免疫抑制治疗早期疗效

Increasing peripheral blood neutrophils after G-CSF treatment is a predictor of early response to immunosuppressive therapy in severe aplastic anemia

目的 探讨重型/极重型再生障碍性贫血（SAA/VSAA）患者免疫抑制治疗（IST）前应用G-CSF治疗后的中性粒细胞反应（ANC反应）对于IST早期疗效的预测价值.方法 回顾性分析2005年9月至2011年11月行IST的SAA/VSAA共125例患者资料,对IST前应用G-CSF治疗后的ANC反应与IST近期疗效进行相关性分析,绘制G-CSF治疗后ANC增高程度（ΔANC）预测IST疗效的ROC曲线.结果 G-CSF治疗后ANC反应组IST后3个月（49.0％对28.9％,P=0.023）及6个月（61.2％对40.8％,P=0.026）血液学反应（HR）率明显高于无反应组;以G-CSF治疗10d内ΔANC≥0.5×10/9L作为ANC反应界值预测IST后3个月及6个月疗效最佳.多因素分析显示G-CSF治疗10d内ANC反应为IST后3个月HR的独立预后因素（P=0.004）,但并非IST后6个月HR的独立预后因素.G-CSF治疗后获ANC反应组患者5年总生存率显著高于无反应组[（92.8±4.0）％对（69.5±6.5）％,P=0.025].结论 IST前G-CSF治疗后的ANC反应可提示骨髓残存造血,是方便、实用的预测患者接受IST早期疗效及长期生存的指标.

Objective To testify whether absolute neutrophil count （ANC） response to preimmunosuppressive-therapy （pre-IST） granulocyte-stimulating factor （G-CSF） treatment could predict early response to IST in severe aplastic anemia （SAA）.Methods Clinical data and hematologic response of 125 SAA patients treated with antithymocyte globulin （r-ATG） combined with cyclosporine were retrospectively analyzed.Correlation of ANC response to pre-IST G-CSF treatment and early response to IST were statistically analyzed,and receiver operating characteristic （ROC） curve was used to estimate the value of increased ANC （Δ ANC） in predicting early IST response.Results The hematologic response （HR） rate to IST in ANC reponded patients was significantly higher than non-responded group （3-month HR 49.0％ vs 28.9％,P=0.023; 6-month HR 61.2％ vs 40.8％,P=0.026）.With ΔANC≥0.5× 109/L as cutoff level,the best point to predict early IST response was 10 days after G-CSF （d 10）.Response of ANC to pre-IST G-CSF treatment at d 10 was among the independent factors of predicting 3-month （P=0.004）,but not for 6-month response to IST.The overall 5-year survival rate was 92.8％ and 69.5％ in ANC responded and non-responed groups,respectively （P=0.025）.Conclusion Responding to pre-IST G-CSF treatment reflected the residual bone marrow hematopoiesis,and could act as a convenient and practical predictor to early IST response as well as long-term survival in SAA.