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肥胖症作为儿童急性淋巴细胞白血病治疗相关毒性的预测因子。

Obesity as a predictor of treatment-related toxicity in children with acute lymphoblastic leukaemia.

机构信息

Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.

Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

出版信息

Br J Haematol. 2022 Mar;196(5):1239-1247. doi: 10.1111/bjh.17936. Epub 2021 Nov 2.

DOI:10.1111/bjh.17936
PMID:34726257
Abstract

Obesity is associated with poor outcomes in childhood acute lymphoblastic leukaemia (ALL). We explored whether severe treatment-related toxicity and treatment delays could explain this observation. This study included 1 443 children aged 2·0-17·9 years with ALL treated with the Nordic Society of Pediatric Haematology and Oncology (NOPHO) ALL2008 non-high-risk protocol. Prospective treatment-related toxicities registered every three-month interval were used. Patients were classified according to sex- and age-adjusted international childhood cut-off values, corresponding to adult body mass index: underweight, <17 kg/m ; healthy weight, 17 to <25 kg/m ; overweight, 25 to <30 kg/m ; and obese, ≥30 kg/m . Obese children had a higher incidence rate ratio (IRR) for severe toxic events {IRR: 1·55 [95% confidence interval (CI) 1·07-2·50]}, liver and kidney failures, bleeding, abdominal complication, suspected unexpected severe adverse reactions and hyperlipidaemia compared with healthy-weight children. Obese children aged ≥10 years had increased IRRs for asparaginase-related toxicities compared with healthy-weight older children: thromboses [IRR 2·87 (95% CI 1·00-8·21)] and anaphylactic reactions [IRR 7·95 (95% CI 2·15-29·37)] as well as higher risk for truncation of asparaginase [IRR 3·54 (95% CI 1·67-7·50)]. The high prevalence of toxicity and a higher risk of truncation of asparaginase may play a role in the poor prognosis of obese children aged ≥10 years with ALL.

摘要

肥胖与儿童急性淋巴细胞白血病(ALL)的不良结局有关。我们探讨了严重的治疗相关毒性和治疗延迟是否可以解释这一观察结果。本研究纳入了 1443 名年龄在 2.0-17.9 岁的 ALL 患儿,他们接受了北欧儿科血液学和肿瘤学会(NOPHO)ALL2008 非高危方案治疗。前瞻性地每 3 个月间隔登记治疗相关毒性。患者根据性别和年龄调整的国际儿童截断值进行分类,相当于成人 BMI:体重不足,<17 kg/m;健康体重,17-<25 kg/m;超重,25-<30 kg/m;肥胖,≥30 kg/m。与健康体重的儿童相比,肥胖儿童严重毒性事件(IRR:1.55[95%置信区间(CI)1.07-2.50])、肝肾功能衰竭、出血、腹部并发症、疑似意外严重不良反应和高脂血症的发生率更高。≥10 岁的肥胖儿童与健康体重的大龄儿童相比,与门冬酰胺酶相关的毒性的 IRR 更高:血栓形成(IRR 2.87[95%CI 1.00-8.21])和过敏反应(IRR 7.95[95%CI 2.15-29.37]),以及门冬酰胺酶截断的风险更高(IRR 3.54[95%CI 1.67-7.50])。毒性高发和门冬酰胺酶截断的风险较高可能是≥10 岁肥胖 ALL 患儿预后不良的原因之一。

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