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芦可替尼对异基因造血干细胞移植后肺功能的影响。

Effect of Ruxolitinib on Lung Function after Allogeneic Stem Cell Transplantation.

机构信息

Pneumology Department, Service de Pneumologie, Université de Paris, Hôpital Saint-Louis, AP-HP, Paris, France.

ECSTRRA Team, Université de Paris, INSERM, UMR 1153 CRESS, Paris, France; Biostatistics and Medical data Department, Service de Biostatistique et Information Médicale, Hôpital Saint-Louis, AP-HP, Paris, France.

出版信息

Biol Blood Marrow Transplant. 2020 Nov;26(11):2115-2120. doi: 10.1016/j.bbmt.2020.07.033. Epub 2020 Jul 29.

Abstract

Ruxolitinib, a selective Janus kinase (JAK)1/2 inhibitor, has recently been proposed for steroid-refractory chronic graft-versus host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT), particularly in severe skin cGVHD. Lung function impairment is common in severe skin cGVHD through concomitant bronchiolitis obliterans syndrome (BOS) or restrictive lung disease (RLD) from skin sclerosis. To date, no treatment has shown a benefit on lung function in this context. We retrospectively assessed the effect of ruxolitinib on lung function in a cohort of 70 patients diagnosed with sclerotic-type skin cGVHD between March 2015 and April 2018. Among these patients, 36 received ruxolitinib. To handle confounding by indication bias, exposure groups were matched on the propensity score to receive ruxolitinib, incorporating age, myeloablative conditioning, total body irradiation, BOS, forced expiratory volume in 1 second (FEV), forced vital capacity (FVC), and tobacco use at the time of cohort entry, as well as the time from transplantation. The 1:1 matching used a greedy-matching algorithm with replacement, with a caliper of 0.10. FVC and FEV trajectories during follow-up were compared in the matched samples, using linear mixed-effects models. The median duration of follow-up of the 46 matched patients was 58 months (interquartile range, 32 to 84 months). Ten patients had an RLD (6 exposed, 4 unexposed), and 13 patients were diagnosed with BOS (8 exposed, 5 unexposed). FEV decreased significantly over time independent of exposure to ruxolitinib (P < .0001). The FEV trajectory was similar in the exposed patients and the unexposed patients (P = .11). In conclusion, ruxolitinib administration did not demonstrate any improvement in the course of respiratory function in allogeneic HSCT recipients with sclerotic-type skin cGVHD.

摘要

芦可替尼是一种选择性 Janus 激酶(JAK)1/2 抑制剂,最近被提议用于异基因造血干细胞移植(HSCT)后类固醇难治性慢性移植物抗宿主病(cGVHD),特别是在严重皮肤 cGVHD 中。严重皮肤 cGVHD 常伴有细支气管炎闭塞综合征(BOS)或由皮肤硬化引起的限制性肺病(RLD),导致肺功能受损。迄今为止,尚无治疗方法显示对这种情况下的肺功能有益。我们回顾性评估了芦可替尼对 70 例 2015 年 3 月至 2018 年 4 月间诊断为硬化型皮肤 cGVHD 患者的肺功能的影响。这些患者中,36 例接受了芦可替尼治疗。为了处理因适应症偏倚引起的混杂,在接受芦可替尼治疗的倾向评分上对暴露组进行了匹配,纳入了年龄、清髓性调理、全身照射、BOS、第 1 秒用力呼气量(FEV)、用力肺活量(FVC)以及队列入组时的吸烟情况,以及从移植到现在的时间。1:1 匹配采用贪婪匹配算法,置换法,卡尺值为 0.10。在匹配样本中,使用线性混合效应模型比较了 FVC 和 FEV 随时间的变化轨迹。46 例匹配患者的中位随访时间为 58 个月(四分位距,32 至 84 个月)。10 例患者患有 RLD(6 例暴露,4 例未暴露),13 例患者被诊断为 BOS(8 例暴露,5 例未暴露)。FEV 随时间显著下降,与芦可替尼暴露无关(P<0.0001)。暴露组患者和未暴露组患者的 FEV 轨迹相似(P=0.11)。总之,芦可替尼治疗并未显示在异基因 HSCT 受者中治疗硬化型皮肤 cGVHD 时对呼吸功能的改善。

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