围免疫抑制治疗期感染对重型再生障碍性贫血患者血液学反应及生存的影响

Effects of peri-immunosupressive therapy period infection on hematologic response and survival of severe aplastic anemia

目的探索围免疫抑制治疗（IST）期（IST前1个月至IST后3个月）感染对重型／极重型再生障碍性贫血（SAA／VSAA）患者IST疗效的影响。方法回顾性分析一线行IST的105例SAA／VSAA患者临床资料，研究围IST期感染特征及其对IST疗效的影响。结果全部105例患者中，97例（92．4％）发生270例次围IST期感染，中位感染2（1～7）次，中位发热7（1～47）d，发病部位以呼吸道最为常见，占35．1％。致病微生物明确的感染96例次（35．6％），共检出169株病原菌，以细菌为主，占88．2％。IST前1个月感染与未感染患者IST后6个月血液学反应率比较差异有统计学意义（50．8％对80．0％，P=0．004）。ROC曲线优化IST后6个月能否获得血液学反应的感染次数界限值为3次，发热时间界限值为4d。全部105例患者5年总生存（OS）率为76％，感染3次及以上患者5年OS率为（59．6±7．2）％，明显低于感染少于3次患者[（89．5±4．0）％]（P〈0．01）；发热时间〉／4d患者5年OS率为（63．4±5．8）％，明显低于发热时间〈4d患者（100．0％）（P〈0．01）。结论IST前1个月感染对IST疗效有影响，同IST期感染3次及以上、发热时间≥4d患者IST血液学反应率低，生存时间短。

Objective To explore the effects ofperi-immunosuppressive treatment （IST） infection on outcomes of severe and very severe aplastic anemia （SAA/VSAA） patients. Methods Medical record and follow-up data of 105 SAA/VSAA who underwent first-line IST were retrospectively analyzed to find out the characters of infections （1 month before to 3 months after IST）, and its effects on hematologic response and survival. Results Of 105 patients, a total of 270 febrile episodes were recorded in 97 patients （92.4%） during their peri-IST periods, with the median infections of 2 （1-7） episodes in each patient with the median febrile duration of 7 （1-47） days. Respiratory system （35.1%） was the primary anatomic site of infection. Bacteria （88.2%） were common causes of total 169 pathogenic bacteria in 96 clear pathogenic bacteria episodes. And patients who got infection 1 month before IST had much lower 6-month hematologic response rate than their counterpart ones （50.8% vs 80.0%, P=0.004）. Multiple febrile episodes （≥3 times） and the total febrile duration ≥4 days showed the best sensitivity and specificity according to the ROC curve analysis. The 5-year overall survival of the 105 patients was 76%. The 5-year OS of patients with multiple febrile episodes （≥3 times） were much lower than their counterpart ones [ （59.6±7.2）% vs （89.5±4.0）%] （P〈 0.01 ）. The 5-year OS of the total febrile duration≥ 4 days was much lower than their counterpart ones [（63.4±5.8）% vs 100.0% ] （P〈 0.01）. Conclusion Infections 1 month before IST were associated with hematologic response. Multiple febrile episodes （≥3 times） and infections with the febrile duration ≥4 days presented inferior hematologic response and survival.