Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Medical Center, New York, New York.
Division of Pediatric Hematology/Oncology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York.
Pediatr Blood Cancer. 2018 Mar;65(3). doi: 10.1002/pbc.26871. Epub 2017 Nov 1.
This study compared the relative incidence of treatment-related toxicities and the event-free and overall survival between Hispanic and non-Hispanic children undergoing therapy for acute lymphoblastic leukemia (ALL) on Dana-Farber Cancer Institute ALL Consortium protocol 05-001.
Secondary analysis of prospectively collected data from a phase III multicenter study in children and adolescents of 1-18 years with previously untreated ALL.
Between 2005 and 2011, 794 eligible patients enrolled on DFCI 05-001, 730 of whom were included in this analysis (19% [N = 150] Hispanic, 73% [N = 580] non-Hispanic). Hispanic patients were more likely to be ≥10 years of age (32% vs. 24%, P = 0.045) at diagnosis. Toxicity analyses revealed that Hispanic patients had significantly lower cumulative incidence of bone fracture (P < 0.001) and osteonecrosis (ON; P = 0.047). In multivariable risk regression, the risk of ON was significantly lower in Hispanic patients ≥10 years (HR 0.23; P = 0.006). Hispanic patients had significantly lower 5-year event-free survival (EFS) (79.4%; 95% CI: 71.6-85.2) and overall survival (OS) (89.2%; 95% CI: 82.7-93.4) than non-Hispanic patients (EFS: 87.5%; 95% CI: 84.5-90.0, P = 0.004; OS: 92.7%; 95% CI: 90.2-94.6, P = 0.006). Exploratory analyses revealed differences between Hispanic and non-Hispanic patients in the frequency of common variants in genes related to toxicity or ALL outcome.
Hispanic children treated for ALL on DFCI 05-001 had fewer bone-related toxicities and inferior survival than non-Hispanic patients. While disease biology is one explanatory variable for outcome disparities, these findings suggest that biologic and non-biologic mechanisms affecting drug delivery and exposure in this population may be important contributing factors as well.
本研究比较了在丹娜-法伯癌症研究所急性淋巴细胞白血病（ALL）联盟方案 05-001 中接受治疗的西班牙裔和非西班牙裔儿童的治疗相关毒性的相对发生率，以及无事件生存和总生存情况。
对一项前瞻性收集的 1 至 18 岁儿童和青少年初治 ALL 的 III 期多中心研究数据进行二次分析。
在 2005 年至 2011 年期间，794 名符合条件的患者在 DFCI 05-001 上登记，其中 730 名患者纳入本分析（19%[N=150]为西班牙裔，73%[N=580]为非西班牙裔）。西班牙裔患者在诊断时年龄≥10 岁的比例更高（32%比 24%，P=0.045）。毒性分析显示，西班牙裔患者发生骨折（P<0.001）和骨坏死（ON；P=0.047）的累积发生率显著降低。在多变量风险回归中，年龄≥10 岁的西班牙裔患者发生 ON 的风险显著降低（HR 0.23；P=0.006）。与非西班牙裔患者相比，西班牙裔患者的 5 年无事件生存（EFS）（79.4%；95%CI：71.6-85.2）和总生存（OS）（89.2%；95%CI：82.7-93.4）显著降低（EFS：87.5%；95%CI：84.5-90.0，P=0.004；OS：92.7%；95%CI：90.2-94.6，P=0.006）。探索性分析显示，在与毒性或 ALL 结局相关的基因的常见变异频率方面，西班牙裔和非西班牙裔患者存在差异。
在 DFCI 05-001 上接受 ALL 治疗的西班牙裔儿童发生与骨骼相关的毒性和生存不良的情况少于非西班牙裔患者。虽然疾病生物学是解释结果差异的一个变量，但这些发现表明，影响该人群药物输送和暴露的生物学和非生物学机制也可能是重要的促成因素。
