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Endothelial Activation and Stress Index (EASIX) at Admission Predicts Fluid Overload in Recipients of Allogeneic Stem Cell Transplantation.
Biology of Blood and Marrow Transplantation ( IF 5.609 ) Pub Date : 2020-02-09 , DOI: 10.1016/j.bbmt.2020.01.028
Ankur Varma 1 , Gabriela Rondon 2 , Samer A Srour 2 , Julianne Chen 2 , Celina Ledesma 2 , Richard E Champlin 2 , Stefan O Ciurea 2 , Rima M Saliba 2
Affiliation  

Fluid overload (FO) grade ≥2 (more than 10% weight gain from baseline) has recently been recognized as an important toxicity associated with a high rate of nonrelapse mortality in recipients of allogeneic hematopoietic cell transplantation (AHCT). The causes for FO remain unclear. We hypothesized that endothelial damage, possibly due to treatments received prior to AHCT, may be associated with this toxicity and sought to determine whether the Endothelial Activation and Stress Index (EASIX) (defined as lactate dehydrogenase [U/L] × creatinine [mg/dL]/platelets [109 cells/L]) correlates with grade ≥2 FO in 2 cohorts of recipients of AHCT at our institution. We tested our hypothesis in a cohort of 145 consecutive recipients (study cohort) of AHCT transplant from HLA-haploidentical donors and validated the findings in a cohort of 449 (validation cohort) recipients of AHCT from HLA-matched donors who underwent transplantation between 2010 and 2015. Predictors of grade ≥2 FO were evaluated using competing risks regression in univariate analysis and classification and regression tree (CART) analysis in multivariate analysis. The cumulative incidence of grade ≥2 FO was estimated considering death as a competing risk. EASIX scores were evaluated based on log2-transformed values. Optimal predictive EASIX cutoff values were determined based on receiver operating characteristics curve analysis. Grade ≥2 FO occurred in 21% and 6% of the study and validation cohorts, respectively, with the majority of these cases being diagnosed before the day of AHCT. Median log2 EASIX score at admission was 2.4 (interquartile range [IQR], 1.3, 3.7) and 2.5 (IQR, 1.4, 3.9) in the 2 respective cohorts. In univariate analysis, high EASIX at admission was a significant predictor of grade ≥2 FO in the study (cutoff: 4.4, hazard ratio [HR] = 4.8, P < .001) and in the validation (cutoff: 4.3, HR = 4.8, P < .001) cohorts. The significant effect of EASIX persisted in multivariate CART analysis in the study (HR = 6.3, P < .001) and the validation (HR = 28, P = .002) cohorts. Additional predictors in multivariate analysis included body weight below 80 kg in recipients older than 55 years (HR = 4.5, P < .001) in the study cohort and diabetes (HR = 34, P = .001) and age >60 years (HR = 9.6, P = .04) in the validation cohort. At admission, the prevalence of EASIX score of >4.3 (18% versus 17%, P = .9) was not different between the diabetics and nondiabetics. EASIX score at admission is a significant predictor of grade ≥2 FO in recipients of AHCT from HLA-haploidentical or HLA-matched donors. Independently of EASIX, older patients with low weight were associated with increased risk of grade ≥2 FO for recipients of HLA-haploidentical transplants. For the HLA-matched cohort, diabetes and older age were associated with increased FO risk. These findings require validation in external cohorts.

中文翻译:

入院时的内皮细胞活化和应激指数(EASIX)预测同种异体干细胞移植受者的液体超负荷。

最近,同种异体造血细胞移植(AHCT)接受者的体液超负荷(FO)≥2级(比基线增加了10%以上的体重)被认为是与非复发死亡率高相关的重要毒性。FO的原因尚不清楚。我们假设内皮损伤可能与这种毒性相关,可能是由于AHCT之前接受的治疗引起的,因此试图确定内皮激活和应激指数(EASIX)(定义为乳酸脱氢酶[U / L]×肌酐[mg / dL] /血小板[109个细胞/ L])与我们机构的2个AHCT接受者队列中≥2 FO相关。我们在来自HLA单倍体供体的145个连续AHCT移植受者(研究队列)队列中检验了我们的假设,并验证了2010年至2006年之间接受HLA匹配供体的449个(验证队列)AHCT接受者队列中的研究结果。 2015年。使用竞争风险回归在单变量分析和分类以及回归树(CART)分析在多变量分析中评估了≥2 FO的预测因素。估计≥2 FO的累积发生率将死亡视为竞争风险。EASIX分数是根据log2转换后的值进行评估的。根据接收器工作特性曲线分析确定最佳的EASIX预测截止值。≥2 FO发生在研究和验证队列中的分别为21%和6%,其中大多数病例是在AHCT当天之前被诊断出来的。两组入组时log2 EASIX的中位数分别为2.4(四分位间距[IQR],1.3、3.7)和2.5(IQR,1.4、3.9)。在单变量分析中,入院时高EASIX是研究中FO≥2的重要预测指标(临界值:4.4,危险比[HR] = 4.8,P <.001)和验证中(临界值:4.3,HR = 4.8) ,P <.001)队列。EASIX的显着效果在该研究的多变量CART分析(HR = 6.3,P <.001)和验证(HR = 28,P = .002)人群中持续存在。多变量分析中的其他预测因素包括研究队列和糖尿病(HR = 34,P = .001)和年龄> 60岁(HR)的55岁以上受试者的体重低于80 kg(HR = 4.5,P <.001)和糖尿病= 9.6,P = .04)。入院时,糖尿病患者和非糖尿病患者的EASIX得分> 4.3(18%比17%,P = 0.9)。入院时的EASIX分数是HLA单倍型或HLA匹配供者的AHCT接受者≥2 FO的重要预测指标。与EASIX无关,低体重的老年患者与HLA单倍体移植接受者的≥2 FO风险增加相关。对于HLA匹配人群,糖尿病和老年与FO风险增加相关。这些发现需要外部队列的验证。与EASIX无关,体重低的老年患者与HLA单倍体移植接受者的≥2 FO风险增加相关。对于HLA匹配人群,糖尿病和老年与FO风险增加相关。这些发现需要外部队列的验证。与EASIX无关,低体重的老年患者与HLA单倍体移植接受者的≥2 FO风险增加相关。对于HLA匹配人群,糖尿病和老年与FO风险增加相关。这些发现需要外部队列的验证。
更新日期:2020-02-09
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