目的: 探讨接受异基因造血干细胞移植(allogeneic stem cell transplantation, allo-SCT)后出现晚发重症肺炎(late-onset severe pneumonia, LOSP)患者的药物治疗情况与肺炎预后转归的关系。方法: 回顾性分析2016年1月至2021年8月在北京大学人民医院接受allo-SCT后出现LOSP的82例患者的治疗药物启用时间, 尤其是抗病毒药物和激素类药物的启用时间与肺炎预后转归的关系。采用Mann-Whitney U检验、χ²检验进行单因素分析, Logistic回归进行多因素分析; χ²检验若涉及多组(n＞2), 其检验水准采用Bonferroni校正。结果: 在82例患者中, LOSP的中位发病时间为移植后220 d(93~813 d), 患者60 d的生存率为58.5%(48/82), 其中好转患者对应的中位好转时间为18 d(7~44 d), 死亡患者的中位死亡时间为22 d(2~53 d)。多因素分析结果显示, 抗病毒药物启用距离LOSP发病的时间(＜10 d vs. ≥10 d, P=0.012)和激素启用距离抗病毒药物的时间(＜10 d vs. ≥10 d, P=0.027)是影响LOSP患者60 d生存情况的因素。根据上述多因素分析结果进一步将患者分为4组: A组(抗病毒＜10 d且激素≥10 d)、B组(抗病毒＜10 d且激素＜10 d)、C组(抗病毒≥10 d且激素≥10 d)和D组(抗病毒≥10 d且激素＜10 d), 其60 d生存率分别为91.7%、56.8%、50.0%和21.4%。结论: 在接受allo-SCT后出现LOSP的患者中, 抗病毒药物及激素类药物的启用时间与肺炎预后相关, 早期加用抗病毒药物且在其后晚加用激素类药物的患者生存率最高, 提示对于病因不明确的LOSP患者需高度怀疑病毒感染继发过度免疫反应的可能。

Objective: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). Methods: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. Results: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. Conclusion: Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.