RAP无激素方案治疗异基因造血干细胞移植后中重度闭塞性细支气管炎综合征的单中心回顾性分析

RAP hormone-free regimen in the treatment of moderate to severe bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation：a single-center retrospective analysis

摘要

目的 回顾性分析RAP无激素方案——“芦可替尼、阿奇霉素、吡非尼酮”治疗异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation，allo-HSCT）后中重度闭塞性细支气管炎综合征（bronchiolitis obliterans syndrome，BOS）的临床疗效及影响因素。 方法 纳入2018年1月1日至2023年12月31日于电子科技大学附属医院·四川省人民医院血液科行allo-HSCT并发生中重度BOS的患者14例，回顾性分析RAP无激素方案——“芦可替尼、阿奇霉素、吡非尼酮”的临床疗效及影响因素。 结果 ①有效率：3、6和12个月治疗总反应率分别为50.0%、57.1%和50.0%。治疗有效的8例患者在6个月时出现1秒用力呼气量（FEV1）%预测值（t=2.187，P=0.033）、6 min步行测试（t=2.338，P=0.023）、ECOG体能状态评分（t=2.681，P=0.013）和慢性移植物抗宿主病（chronic graft-versus-host disease，cGVHD）严重程度（Z=2.155，P=0.032）的明显改善。②生存：中位随访13（5，64）个月，5例（35.7%）死亡，死因为重症肺炎并发症。单因素分析提示RAP疗程延长与生存改善趋势相关（Wald值=2.892，P=0.089）。③激素暴露：14例均有长期糖皮质激素使用史，8例（57.1%）1个月内停用，2例（14.3%）减量50%以上。④安全性良好，主要不良反应为3级以下胃肠道反应及血液学毒性。 结论 RAP无激素方案治疗allo-HSCT后中重度BOS显示良好疗效，允许快速停用糖皮质激素，提高患者生活质量和长期生存。但限于小样本量和回顾性设计，有待前瞻性研究进一步验证。

Abstract

Objective To retrospectively analyze the clinical efficacy of the RAP（Ruxolitinib，Azithromycin，and Pirfenidone） hormone-free regimen in the treatment of moderate to severe BOS and its influencing factors. Methods This study included 14 patients who developed moderate to severe BOS after undergoing allo-HSCT at our center from January 1，2018 to December 31，2023. These patients were retrospectively analyzed for the clinical efficacy of the RAP hormone-free regimen and its influencing factors. Results ①The overall response rates at 3，6 and 12 months of treatment were 50.0%，57.1%，and 50.0%，respectively. At the six-months post RAP regimen，the FEV1% predicted value（t=2.187，P=0.033），6 minute walk test（t=2.338，P=0.023），ECOG physical state score（t=2.681，P=0.013） and cGVHD severity（Z=2.155，P=0.032） of 8 patients who responded to the RAP treatment were significantly improved. ②Survival： During a median follow-up of 13 months，5 patients（35.7%） died of severe pneumonia complications. Univariate analysis showed that the extended course of RAP treatment was correlated with a trend of survival improvement（P=0.089）. ③Glucocorticoid exposure：all 14 cases had a long-term history of glucocorticoid use，8 cases（57.1%） discontinued glucocorticoid use within 1 month，and 2 cases reduced their dose by more than 50%. ④The safety profile was favorable，and the main adverse reactions were gastrointestinal reactions and hematological toxicity. Conclusion The RAP hormone-free regimen shows a favorable effect in the treatment of moderate to severe BOS. It allows for the rapid withdrawal of glucocorticoids and improves the quality of life and long-term survival of patients. However，it needs to be further verified by prospective studies due to its small sample size and retrospective design.

关键词

无激素方案 / 异基因造血干细胞移植 / 闭塞性细支气管炎综合征 / 回顾性分析

Key words

hormone-free regimen / allogeneic hematopoietic stem cell transplantation / bronchiolitis obliterans syndrome / retrospective analysis

基金资助

四川省科技厅重点研发资助项目(2023YFS0207;2022YFS0367)