Bray G L, Muenz L, Makris N, Lessin L S
Department of Pediatrics, George Washington University School of Medicine, Washington, DC.
Am J Pediatr Hematol Oncol. 1994 Feb;16(1):50-4.
Although it is clear that sickle cell disease is curable with bone marrow transplantation, there are few objective criteria that are helpful in the identification of suitable candidates for this aggressive and potentially life-threatening procedure. This disease is characterized by a highly variable clinical course, and there is a need to intervene with marrow transplant before the onset of disease-mediated chronic organ damage. These factors high-light the need for a clinical severity index that can prospectively identify patients who are at high risk for a turbulent clinical course and a poor prognosis.
We used the Cooperative Study of Sickle Cell Disease data base to identify features of the disease in early childhood (i.e., < 2 years of age) that are associated either with significant morbidity later in childhood or early mortality. Our study population includes the 1,944 children who entered the study before 12 years of age. Univariate analysis showed that factors associated with the occurrence of cerebrovascular accident (51 patients) include hematocrit, rate of change of pocked red cell count, and polymer fraction at 40% oxygen saturation (PF40). Only low hematocrit was predictive of death in this pediatric cohort (45 disease-related deaths).
Our ability to identify other potential factors that correlate with these outcome measures is limited by their small numbers. Hence, it was necessary to designate a different endpoint whose relationship with various clinical and laboratory parameters could be assessed. To accomplish this, a distribution of acute events, which were defined as any episode of pain or acute chest syndrome, was calculated. Also, the age-specific "expected" event rate, defined as the mean number of events per patient-year of observation, was determined.
The relationship between various aspects of sickle cell disease and high positive deviance from the expected event rate will be assessed in a cohort of 519 children who entered the study prior to 7 months of age and were followed beyond their second birthday.
尽管镰状细胞病可通过骨髓移植治愈这一点很明确，但几乎没有客观标准有助于识别适合进行这种激进且可能危及生命的手术的候选人。这种疾病的临床病程高度可变，需要在疾病介导的慢性器官损伤发生之前进行骨髓移植干预。这些因素凸显了需要一种临床严重程度指数，能够前瞻性地识别出临床病程动荡且预后不良的高危患者。
我们利用镰状细胞病合作研究数据库来确定儿童早期（即<2岁）与儿童期后期显著发病或早期死亡相关的疾病特征。我们的研究人群包括1944名12岁之前进入该研究的儿童。单因素分析表明，与脑血管意外发生（51例患者）相关的因素包括血细胞比容、有核红细胞计数变化率以及40%氧饱和度下的聚合物分数（PF40）。在这个儿科队列中，只有低血细胞比容可预测死亡（45例与疾病相关的死亡）。
我们识别与这些结局指标相关的其他潜在因素的能力受到其数量较少的限制。因此，有必要指定一个不同的终点，其与各种临床和实验室参数的关系可以进行评估。为实现这一点，计算了定义为任何疼痛发作或急性胸综合征发作的急性事件分布。此外，还确定了年龄特异性的“预期”事件率，定义为每位患者每年观察的平均事件数。
将在519名7个月龄之前进入研究且随访至两岁以后的儿童队列中评估镰状细胞病各方面与预期事件率的高正偏差之间的关系。
