Cheng Guang-Shing, Bondeelle Louise, Gooley Ted, He Qianchuan, Jamani Kareem, Krakow Elizabeth F, Flowers Mary E D, de Latour Régis Peffault, Michonneau David, Socié Gérard, Chien Jason W, Chevret Sylvie, Bergeron Anne
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington.
AP-HP, Université de Paris, Hôpital Saint-Louis, Service de Pneumologie, Paris, France.
Biol Blood Marrow Transplant. 2020 Feb;26(2):392-400. doi: 10.1016/j.bbmt.2019.10.025. Epub 2019 Nov 1.
Azithromycin exposure during the early phase of allogeneic hematopoietic cell transplantation (HCT) has been associated with an increased incidence of hematologic relapse. We assessed the impact of azithromycin exposure on the occurrence of relapse or new subsequent neoplasm (SN) in patients with bronchiolitis obliterans syndrome (BOS) after HCT who are commonly treated with azithromycin alone or in combination with other agents. In a retrospective study of patients with BOS from 2 large allograft centers, the effect of azithromycin exposure on the risk of relapse or SN was estimated from a Cox model with a time-dependent variable for treatment initiation. The Cox model was adjusted on time-fixed covariates measured at cohort entry, selected for their potential prognostic value. Similar models were used to assess the exposure effect on the cause-specific hazard of relapse, SN, and death free of those events. Sensitivity analyses were performed using propensity score matching. Among 316 patients, 227 (71.8%) were exposed to azithromycin after BOS diagnosis. The corresponding adjusted hazard ratio (HR) in patients exposed to azithromycin versus unexposed was 1.51 (95% confidence interval [CI], 0.90 to 2.55) for relapse or SN, 0.82 (95% CI, 0.37 to 1.83) for relapse, and 2.00 (95% CI, 1.01 to 3.99) for SN. Patients exposed to azithromycin had a significantly lower cause-specific hazard of death free of neoplasm and relapse (adjusted HR, 0.54; 95% CI, 0.34 to 0.89). In conclusion, exposure to azithromycin after BOS after HCT was associated with an increased risk of SN but not relapse.
在异基因造血细胞移植（HCT）早期接触阿奇霉素与血液学复发发生率增加有关。我们评估了阿奇霉素暴露对HCT后患有闭塞性细支气管炎综合征（BOS）的患者复发或新的后续肿瘤（SN）发生的影响，这些患者通常单独使用阿奇霉素或与其他药物联合治疗。在一项对来自2个大型同种异体移植中心的BOS患者的回顾性研究中，通过具有治疗开始时间依赖性变量的Cox模型估计阿奇霉素暴露对复发或SN风险的影响。Cox模型根据队列入组时测量的时间固定协变量进行调整，这些协变量因其潜在的预后价值而被选择。类似的模型用于评估暴露对复发、SN和无这些事件的死亡的病因特异性风险的影响。使用倾向评分匹配进行敏感性分析。在316例患者中，227例（71.8%）在BOS诊断后接触了阿奇霉素。接触阿奇霉素与未接触阿奇霉素的患者相比，复发或SN的相应调整后风险比（HR）为1.51（95%置信区间[CI]，0.90至2.55），复发的HR为0.82（95%CI，0.37至1.83），SN的HR为2.00（95%CI，1.01至3.99）。接触阿奇霉素的患者无肿瘤和复发的病因特异性死亡风险显著降低（调整后HR，0.54；95%CI，0.34至0.89）。总之，HCT后BOS患者接触阿奇霉素与SN风险增加有关，但与复发无关。
