Department of Preventive Medicine, Universidade Federal do Rio de Janeiro, Brazil.
Clin Infect Dis. 2012 Jun;54(12):e173-83. doi: 10.1093/cid/cis298. Epub 2012 Mar 15.
Invasive aspergillosis (IA) is a life-threatening infection for immunocompromised patients. Improvement in IA outcome has been hampered by lack of early prognostic factors, namely, those available before starting chemotherapy (baseline) or early in the course of IA (nonbaseline). We hypothesized that prognostic factors can be identified before chemotherapy, ≤7 days from the first positive serum Aspergillus galactomannan index (s-GMI).
We analyzed 98 patients with multiple myeloma who developed neutropenia-related IA and had a positive s-GMI. Three response criteria were used: kinetics of s-GMI, European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definitions, and 6-week survival. Baseline and nonbaseline variables were analyzed separately.
Independent response predictors at baseline were a platelet count ≥65,000 platelets/mm(3) (odds ratio [OR], 1.009; 95% confidence interval [CI], 1.001-1.017; P = .03) by s-GMI kinetics, and a platelet count ≥65,000 platelets/mm(3) (OR, 1.009; 95% CI, 1.002-1.017; P = .01) and a creatinine clearance rate ≥53 mL/min (OR, 1.024; 95% CI, 1.006-1.042; P = .009) by EORTC/MSG criteria, with response rates of 83% and 28% when both variables were above or below these cutoffs, respectively (P < .001). Only baseline creatinine clearance rate ≥53 mL/min predicted 6-week survival (P = .003). Normalization of the s-GMI ≤7 days after the first positive s-GMI and neutrophil recovery were the nonbaseline factors associated with positive outcomes.
Two simple, inexpensive to measure, widely available, and routinely collected prechemotherapy values, platelet count and creatinine clearance rate, predict IA outcome and stratify patients into low-, intermediate-, and high-risk categories, while early evaluation of s-GMI allows timely treatment modification. These findings may improve patient outcomes by optimizing management strategies for this serious infection and may prove valuable in designing clinical trials of interventions to improve IA outcomes.
侵袭性曲霉病（IA）是免疫功能低下患者的一种危及生命的感染。由于缺乏早期预后因素，IA 预后的改善受到了阻碍，这些因素是在开始化疗之前（基线）或在 IA 病程早期（非基线）获得的。我们假设可以在化疗前，即在首次阳性血清曲霉半乳甘露聚糖指数（s-GMI）后 7 天内确定预后因素。
我们分析了 98 例患有多发性骨髓瘤并发生中性粒细胞减少相关 IA 且 s-GMI 阳性的患者。使用了三种反应标准：s-GMI 的动力学、欧洲癌症研究与治疗组织/侵袭性真菌感染合作组和美国国家过敏与传染病研究所真菌病研究组（EORTC/MSG）的定义以及 6 周生存率。分别分析了基线和非基线变量。
基线时独立的反应预测因素是血小板计数≥65,000 个/ mm3（比值比 [OR]，1.009；95%置信区间 [CI]，1.001-1.017；P=.03）通过 s-GMI 动力学，以及血小板计数≥65,000 个/ mm3（OR，1.009；95%CI，1.002-1.017；P=.01）和肌酐清除率≥53 mL/min（OR，1.024；95%CI，1.006-1.042；P=.009）根据 EORTC/MSG 标准，当两个变量均高于或低于这些临界值时，反应率分别为 83%和 28%（P <.001）。只有基线时的肌酐清除率≥53 mL/min 可预测 6 周生存率（P=.003）。s-GMI 在首次阳性 s-GMI 后 7 天内正常化和中性粒细胞恢复是非基线因素，与良好的结果相关。
两种简单、易于测量、广泛可用且常规收集的化疗前值，即血小板计数和肌酐清除率，可以预测 IA 的结果，并将患者分为低、中、高危类别，而 s-GMI 的早期评估可允许及时调整治疗。这些发现可能通过优化对这种严重感染的管理策略来改善患者的预后，并可能在设计改善 IA 结果的干预措施临床试验中具有价值。
