Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.
Survivorship and Inequality in Cancer, Danish Cancer Society Research Center, Copenhagen, Denmark.
Pediatr Blood Cancer. 2022 Jul;69(7):e29508. doi: 10.1002/pbc.29508. Epub 2021 Dec 21.
Socioeconomic differences in survival among children with acute lymphoblastic leukemia (ALL) have been reported in high-income countries and there is an unmet need for strategies to identify vulnerable patient subgroups. Reported differences in survival for children from families with different socioeconomic positions seem to arise when starting maintenance therapy. This could reflect reduced physician's compliance or family adherence to maintenance therapy.
This nationwide cohort study with extensive monitoring of systemic methotrexate (MTX)/6-mercaptopurine (6MP) dosing and metabolite levels, retrospectively investigated 173 Danish children treated according to The Nordic Society for Pediatric Hematology and Oncology ALL2008 protocol from 2008 to 2016.
Significantly lower prescribed doses of MTX and 6MP were seen in the children in families with short parental education (short vs. medium vs. higher education: mMTX: 13.8, 16.2, and 18.6 mg/m /week; p < .01; m6MP: 47.4, 64.9, and 66.1 mg/m /day; p = .03) or parents unemployed/not in workforce (unemployed/not in workforce vs. mixed vs. at work: mMTX: 15.0, 19.9, and 17.2 mg/m /week; p < .01; m6MP: 54.8, 72.0, and 65.1 mg/m /day; p < .01). When assessing family adherence by analyzing MTX and 6MP metabolite levels, including per prescribed dose of MTX and 6MP, we found no significant differences by levels of parental education, affiliation to work market, or income (p > .05 for all comparisons).
These results indicate that inferior physician compliance to protocol recommendations on drug dosage rather than families' adherence to therapy may contribute to the association between socioeconomic position and cure rates in childhood ALL, although precise mechanisms remain to be explored.
在高收入国家已经报道了儿童急性淋巴细胞白血病(ALL)的生存存在社会经济差异,因此需要制定策略来确定弱势患者亚组。来自不同社会经济地位家庭的儿童在开始维持治疗时出现的生存差异报告似乎反映了医生遵守或家庭遵守维持治疗的减少。
本项全国性队列研究对系统甲氨蝶呤(MTX)/6-巯基嘌呤(6MP)剂量和代谢物水平进行了广泛监测,回顾性分析了 173 名根据北欧儿科血液学和肿瘤学会 ALL2008 方案于 2008 年至 2016 年接受治疗的丹麦儿童。
在父母受教育程度较短(短 vs. 中 vs. 高:mMTX:13.8、16.2 和 18.6mg/m/周;p<.01;m6MP:47.4、64.9 和 66.1mg/m/天;p=.03)或父母失业/未就业(失业/未就业 vs. 混合 vs. 工作:mMTX:15.0、19.9 和 17.2mg/m/周;p<.01;m6MP:54.8、72.0 和 65.1mg/m/天;p<.01)的儿童中,MTX 和 6MP 的处方剂量明显较低。当通过分析 MTX 和 6MP 代谢物水平来评估家庭依从性时,包括按 MTX 和 6MP 的规定剂量评估,我们发现父母教育水平、就业市场关系或收入水平无显著差异(所有比较 p>.05)。
这些结果表明,较差的医生遵守药物剂量方案建议而不是家庭对治疗的依从性可能是儿童 ALL 中社会经济地位与治愈率之间关联的原因,尽管确切机制仍有待探讨。