Pollock B H, DeBaun M R, Camitta B M, Shuster J J, Ravindranath Y, Pullen D J, Land V J, Mahoney D H, Lauer S J, Murphy S B
University of Florida, and Pediatric Oncology Group Statistical Office, Gainesville, FL, USA.
J Clin Oncol. 2000 Feb;18(4):813-23. doi: 10.1200/JCO.2000.18.4.813.
We conducted a historic cohort study to test the hypothesis that, after adjustment for biologic factors, African-American (AA) children and Spanish surname (SS) children with newly diagnosed B-precursor acute lymphoblastic leukemia had lower survival than did comparable white children.
From 1981 to 1994, 4,061 white, 518 AA, and 507 SS children aged 1 to 20 years were treated on three successive Pediatric Oncology Group multicenter randomized clinical trials.
AA and SS patients were more likely to have adverse prognostic features at diagnosis and lower survival than were white patients. The 5-year cumulative survival rates were (probability +/- SE) 81.9% +/- 0.6%, 68.6% +/- 2.1%, and 74.9% +/- 2.0% for white, AA, and SS children, respectively. Adjusting for age, leukocyte count, sex, era of treatment, and leukemia blast cell ploidy, we found that AA children had a 42% excess mortality rate compared with white children (proportional hazards ratio [PHR] = 1.42; 95% confidence interval [CI], 1.12 to 1. 80), and SS children had a 33% excess mortality rate compared with white children (PHR = 1.33; 95% CI, 1.19 to 1.49).
Clinical presentation, tumor biology, and deviations from prescribed therapy did not explain the differences in survival and event-free survival that we observed, although differences seem to be diminishing over time with improvements in therapy. The disparity in outcome for AA and SS children is most likely related to variations in chemotherapeutic response to therapy and not to compliance. Further improvements in outcome may require individualized dosing based on specific pharmacogenetic profiles, especially for AA and SS children.
我们开展了一项历史性队列研究,以检验以下假设:在对生物学因素进行调整后,新诊断为B前体急性淋巴细胞白血病的非裔美国(AA)儿童和西班牙姓氏(SS)儿童的生存率低于可比的白人儿童。
1981年至1994年,4061名1至20岁的白人、518名AA儿童和507名SS儿童在三项连续的儿科肿瘤学组多中心随机临床试验中接受治疗。
AA和SS患者在诊断时更有可能具有不良预后特征,且生存率低于白人患者。白人、AA和SS儿童的5年累积生存率分别为(概率±标准误)81.9%±0.6%、68.6%±2.1%和74.9%±2.0%。在对年龄、白细胞计数、性别、治疗时代和白血病原始细胞倍性进行调整后,我们发现AA儿童的死亡率比白人儿童高42%(比例风险比[PHR]=1.42;95%置信区间[CI],1.12至1.80),SS儿童的死亡率比白人儿童高33%(PHR=1.33;95%CI,1.19至1.49)。
临床表现、肿瘤生物学以及与规定治疗的偏差并不能解释我们观察到的生存率和无事件生存率的差异,尽管随着治疗的改善,差异似乎在随着时间的推移而减小。AA和SS儿童预后的差异最有可能与化疗反应的差异有关,而不是与依从性有关。进一步改善预后可能需要根据特定的药物遗传学特征进行个体化给药,尤其是对于AA和SS儿童。