Department of Hematology Oncology, University of Pavia Medical School & Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.
Haematologica. 2011 Mar;96(3):441-9. doi: 10.3324/haematol.2010.033506. Epub 2010 Dec 6.
The incidence of myelodysplastic syndromes increases with age and a high prevalence of co-morbid conditions has been reported in these patients. So far, risk assessment in myelodysplastic syndromes has been mainly based on disease status. We studied the prognostic impact of comorbidity on the natural history of myelodysplastic syndrome with the aim of developing novel tools for risk assessment. The study population included a learning cohort of 840 patients diagnosed with myelodysplastic syndrome in Pavia, Italy, and a validation cohort of 504 patients followed in Duesseldorf, Germany. Information on comorbidity was extracted from detailed review of the patients' medical charts and laboratory values at diagnosis and during the course of the disease. Univariable and multivariable survival analyses with both fixed and time-dependent covariates were performed using Cox's proportional hazards regression models. Comorbidity was present in 54% of patients in the learning cohort. Cardiac disease was the most frequent comorbidity and the main cause of non-leukemic death. In multivariable analysis, comorbidity had a significant impact on both non-leukemic death (P=0.01) and overall survival (P=0.02). Cardiac, liver, renal, pulmonary disease and solid tumors were found to independently affect the risk of non-leukemic death. A time-dependent myelodysplastic syndrome-specific comorbidity index (MDS-CI) was developed for predicting the effect of comorbidity on outcome. This identified three groups of patients which showed significantly different probabilities of non-leukemic death (P<0.001) and survival (P=0.005) also in the validation cohort. Landmark survival analyses at fixed time points from diagnosis showed that the MDS-CI can better define the life expectancy of patients with myelodysplastic syndrome stratified according to the WHO-classification based Prognostic Scoring System (WPSS).Comorbidities have a significant impact on the outcome of patients with myelodysplastic syndrome. Accounting for both disease status by means of the WPSS and comorbidity through the MDS-CI considerably improves risk stratification in myelodysplastic syndromes.
骨髓增生异常综合征的发病率随年龄增长而增加，这些患者常伴有多种合并症。迄今为止，骨髓增生异常综合征的风险评估主要基于疾病状态。我们研究了合并症对骨髓增生异常综合征自然病程的预后影响，旨在开发新的风险评估工具。研究人群包括意大利帕维亚诊断为骨髓增生异常综合征的学习队列中的 840 名患者和德国杜塞尔多夫随访的验证队列中的 504 名患者。合并症信息是从患者的病历和诊断时及疾病过程中的实验室值的详细审查中提取的。使用 Cox 比例风险回归模型进行单变量和多变量生存分析，并使用固定和时变协变量。学习队列中 54%的患者存在合并症。心脏病是最常见的合并症，也是非白血病死亡的主要原因。多变量分析显示，合并症对非白血病死亡（P=0.01）和总生存（P=0.02）均有显著影响。心脏、肝脏、肾脏、肺部疾病和实体瘤被发现独立影响非白血病死亡的风险。为预测合并症对预后的影响，开发了一个基于时间的骨髓增生异常综合征特异性合并症指数（MDS-CI）。该指数确定了三组患者，在验证队列中，这些患者的非白血病死亡率（P<0.001）和生存率（P=0.005）也有显著差异。在固定时间点从诊断开始的 landmark 生存分析表明，MDS-CI 可以更好地定义根据世界卫生组织（WHO）基于预后评分系统（WPSS）的分类分层的骨髓增生异常综合征患者的预期寿命。合并症对骨髓增生异常综合征患者的预后有显著影响。通过 WPSS 考虑疾病状态，通过 MDS-CI 考虑合并症，可以显著改善骨髓增生异常综合征的风险分层。
