Late acute graft-versus-host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors
Late acute graft-versus-host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors
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DOI：
10.1182/blood-2015-09-669846
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发表时间：
2016-11-10
期刊：
影响因子：
20.3
通讯作者：
Pidala, Joseph
中科院分区：
文献类型：
--
作者：
Holtan, Shernan G.;Khera, Nandita;Pidala, Joseph
晚期急性（LA）移植物抗宿主病（GVHD）是在异基因造血细胞移植（HCT）后> 100天发生的持续性、复发性或新发急性GVHD症状。本分析的目的是描述LA GVHD的发病、病程、发病率和死亡率，并研究与LA GVHD相关的血管生成因素。作为慢性GVHD联盟内观察性研究的一部分，招募了一组前瞻性患者（n 5 909）。83例患者（11%）在HCT后中位数160（四分位距，128-204）天发生LA GVHD。尽管83例患者中有51例（61%）在28天内对初始治疗达到完全或部分缓解，但中位无失败生存期仅为7.1个月（95%置信区间为3.4-19.1个月），2年估计总生存率（OS）为56%。鉴于最近描述的经典急性GVHD中循环血管生成因子的改变，我们研究了这些因子的改变是否可以在LA GVHD中识别。我们首先测试了来自慢性GVHD联盟的病例（n=55）和对照组（n=50），然后验证了来自西奈山急性GVHD国际联盟的37例病例的结果。血浆双调蛋白（AREG;表皮生长因子[EGF]受体配体）升高，AREG/EGF比值等于或高于中位数与两个队列中OS较低和非复发死亡率增加相关。典型急性GVHD中检测到AREG升高，但慢性GVHD中未检测到AREG升高。这些前瞻性数据表征了LA GVHD的临床过程，并证明了血管生成因子的改变，使LA GVHD在生物学上不同于慢性GVHD。
Late acute (LA) graft-versus-host disease (GVHD) is persistent, recurrent, or new-onset acute GVHD symptoms occurring > 100 days after allogeneic hematopoietic cell transplantation (HCT). The aim of this analysis is to describe the onset, course, morbidity, and mortality of and examine angiogenic factors associated with LA GVHD. A prospective cohort of patients (n 5 909) was enrolled as part of an observational study within the Chronic GVHD Consortium. Eighty-three patients (11%) developed LA GVHD at a median of 160 (interquartile range, 128-204) days after HCT. Although 51 out of 83 (61%) achieved complete or partial response to initial therapy by 28 days, median failure-free survival was only 7.1 months (95% confidence interval, 3.4-19.1 months), and estimated overall survival (OS) at 2 years was 56%. Given recently described alterations of circulating angiogenic factors in classic acute GVHD, we examined whether alterations in such factors could be identified in LA GVHD. We first tested cases (n=55) and controls (n=50) from the Chronic GVHD Consortium and then validated the findings in 37 cases from Mount Sinai Acute GVHD International Consortium. Plasma amphiregulin (AREG; an epidermal growth factor [EGF] receptor ligand) was elevated, and an AREG/EGF ratio at or above the median was associated with inferior OS and increased nonrelapse mortality in both cohorts. Elevation of AREG was detected in classic acute GVHD, but not chronic GVHD. These prospective data characterize the clinical course of LA GVHD and demonstrate alterations in angiogenic factors that make LA GVHD biologically distinct from chronic GVHD.