Service des Maladies du Sang, Hôpital Huriez, CHU Lille, Lille, France.
CHU de Lille, Université de Lille, INSERM Infinite U1285, Lille, France.
Ann Pharmacother. 2022 Sep;56(9):1007-1015. doi: 10.1177/10600280211068177. Epub 2022 Jan 11.
Defibrotide is indicated for patients who develop severe sinusoidal obstructive syndrome following allogeneic hematopoietic cell transplantation (allo-HCT). Preclinical data suggested that defibrotide carries a prophylactic effect against acute graft-versus-host disease (aGVHD).
The purpose of this study was to investigate the effect of defibrotide on the incidence and severity of aGVHD.
This single-center retrospective study included all consecutive transplanted patients between January 2014 and December 2018. A propensity score based on 10 predefined confounders was used to estimate the effect of defibrotide on aGVHD via inverse probability of treatment weighting (IPTW).
Of the 482 included patients, 64 received defibrotide (defibrotide group) and 418 did not (control group). Regarding main patient characteristics and transplantation modalities, the two groups were comparable, except for a predominance of men in the defibrotide group. The median age was 55 years (interquartile range [IQR]: 40-62). Patients received allo-HCT from HLA-matched related donor (28.6%), HLA-matched unrelated donor (50.8%), haplo-identical donor (13.4%), or mismatched unrelated donor (7.0%). Stem cell source was either bone marrow (49.6%) or peripheral blood (50.4%). After using IPTW, exposure to defibrotide was not significantly associated with occurrence of aGVHD (HR = 0.97; 95% CI 0.62-1.52; = .9) or occurrence of severe aGVHD (HR = 1.89, 95% CI: 0.98-3.66; = .058).
Defibrotide does not seem to have a protective effect on aGVHD in patients undergoing allo-HCT. Based on what has been reported to date and on these results, defibrotide should not be considered for the prevention of aGVHD outside clinical trials.
地塞米松用于治疗异基因造血细胞移植（allo-HCT）后发生严重窦状阻塞综合征的患者。临床前数据表明，地塞米松对急性移植物抗宿主病（aGVHD）具有预防作用。
本研究旨在探讨地塞米松对 aGVHD 发生率和严重程度的影响。
这是一项单中心回顾性研究，纳入了 2014 年 1 月至 2018 年 12 月期间所有连续接受移植的患者。通过逆概率治疗加权（IPTW），基于 10 个预先定义的混杂因素的倾向评分来估计地塞米松对 aGVHD 的影响。
在纳入的 482 例患者中，64 例接受了地塞米松（地塞米松组），418 例未接受（对照组）。除了地塞米松组中男性居多外，两组患者的主要患者特征和移植方式相似。中位年龄为 55 岁（四分位距[IQR]：40-62）。患者接受 HLA 匹配的亲缘供者（28.6%）、HLA 匹配的无关供者（50.8%）、半相合供者（13.4%）或不匹配的无关供者（7.0%）的allo-HCT。干细胞来源为骨髓（49.6%）或外周血（50.4%）。使用 IPTW 后，地塞米松暴露与 aGVHD 的发生（HR = 0.97；95%CI 0.62-1.52； =.9）或严重 aGVHD 的发生（HR = 1.89，95%CI：0.98-3.66； =.058）无显著相关性。
地塞米松似乎不能预防 allo-HCT 患者发生 aGVHD。基于迄今为止的报告和这些结果，地塞米松不应在临床试验之外被考虑用于预防 aGVHD。
