Objective: To explore the characteristics of delayed hematologic response in very/severe aplastic anemia (V/SAA) patients who were treated with immunosuppressive treatment (IST) as first-line approach, and investigate the rationality of early salvage treatment in refractory patients. Methods: The data of V/SAA patients front-line treated with IST were retrospectively analyzed. Delayed response was defined as acquiring hematologic response between 6 and 12 months after 1 course of IST. The clinical as well as hematologic characteristics of the delayed responded patients were investigated. Results: Of the 533 patients, 45 (8.44%, 45/533) were delayed hematologic responders, which accounted for 29.03% (45/155) of the whole non-responders at 6 months. The quality of response in delayed responders analyzed at 12 months (χ2=62.616, P <0.001) and at the end of follow-up (χ2=6.299, P=0.043) was significantly worse than that of robust response group. There were more VSAA patients in delayed response group compared with robust response group (57.8% vs 38.3%, P=0.013), and all the baseline absolute reticulocyte (ARC) count, ARC proportion and absolute neutrophil count (ANC) were much lower than that in delayed response group. Multivariate analysis about the above 2 groups showed that the baseline ARC count <10×109/L significanty reduced the chance of hematologic response within 6 months [OR=3.641(95% CI 1.718-7.719) , P=0.001], and not any factor was found to predict delayed hematologic response in non-responders at 6 months. The 5-year overall survival of 76.50% (95% CI 71.6%-81.4%) and event free survival of 29.10%(95% CI 25.2%-33.0% ) in non-responders at 6 months, both were worse than 97.6% (95% CI 96.6%-98.6% ) and 84.0% (95% CI 81.1%-86.9% ) (P <0.001) of robust response group. Conclusion: The incidence of delayed hematologic response in V/SAA patients by IST is low. The quality of delayed response is not satisfactory and there is no effective means to predict the delayed response. It is reasonable to carry out salvage treatment as early as possible.
目的: 分析极重型／重型再生障碍性贫血（V/SAA）患者一线免疫抑制治疗（IST）迟发血液学反应特征，探讨难治性V/SAA尽早二次治疗的合理性。
方法: 回顾性分析一线接受IST的533例V/SAA患者临床资料，定义IST后6个月内获得血液学反应为应时反应，定义6~12个月获得血液学反应为迟发反应，观察迟发反应的发生率、血液学反应质量及其影响因素。
结果: 533例患者中，45例（8.44%）获得迟发反应，占未获得应时反应且继续接受环孢素A治疗患者的29.03%（45/155）。至IST后12个月及随访结束时迟发反应组血液学反应质量均劣于应时反应组（χ2=62.616，P<0.001和χ2= 6.299，P=0.043）。迟发反应组VSAA患者比例高于应时反应组（57.8％对38.3%，P=0.013），外周血网织红细胞（ARC）比例、ARC计数以及ANC更低，多因素分析显示治疗前ARC<10×109/L的患者获得应时反应的机会明显减少[OR=3.641(95% CI 1.1718~7.719），P=0.001]；未发现独立预测IST后6个月无效患者获得迟发血液学反应的因素。6个月未获血液学反应患者5年总生存率为76.50%（95% CI 71.6%~81.4%）、无事件生存率为29.10%（95% CI 25.2%~33.0%），均显著低于应时反应组患者的97.6%（95% CI 96.6%~98.6%）、84.0%（95% CI 81.1%~86.9%）（P值均<0.001）。
结论: V/SAA患者IST获得迟发血液学反应难以预测，比例较小，疗效质量相对较差。难治性V/SAA患者尽早进行挽救治疗是合理的。