Imperial College London, London, United Kingdom;
Institute of Child Health, University College London, United Kingdom;
Blood. 2014 Aug 14;124(7):1056-61. doi: 10.1182/blood-2014-03-560847. Epub 2014 Jun 5.
Although infection is the major cause of treatment-related mortality (TRM) in childhood acute lymphoblastic leukemia, factors associated with infection-related mortality (IRM) are poorly understood. To address this, we report an analysis of all 75 cases of IRM in the United Kingdom Childhood Acute Lymphoblastic Leukaemia Randomised Trial 2003 (UKALL 2003). The 5-year cumulative incidence of IRM was 2.4% (95% confidence interval [CI], 1.9%-3.0%), accounting for 75 (30%) of 249 trial deaths and 75 (64%) of 117 TRM deaths. Risk for IRM as a proportion of TRM was greater in induction than other phases (77% vs 56%; P = .02). Sixty-eight percent of cases were associated with bacterial infection (64% Gram-negative) and 20% with fungal infection. Down syndrome was the most significant risk factor for IRM (odds ratio [OR], 12.08; 95% CI, 6.54-22.32; P < .0001). In addition, there was a trend toward increased IRM in girls (OR, 1.63; 95% CI, 1.02-2.61; P = .04), as well as increasing treatment intensity (regimen B vs A: OR, 2.11 [95% CI, 1.24-3.60]; regimen C vs A: OR, 1.41 [95% CI, 0.76-2.62]; P = .02). Importantly, patients with Down syndrome were at significantly higher risk for IRM during maintenance (P = .048). Our results confirm Down syndrome as a major risk factor for IRM. Enhanced supportive care and prophylactic antibiotics should be considered in high-risk patient groups and during periods of increased risk. This study was registered at http://www.controlled-trials.com/ as #ISRCTN07355119.
虽然感染是儿童急性淋巴细胞白血病治疗相关死亡率（TRM）的主要原因，但与感染相关死亡率（IRM）相关的因素仍了解甚少。为了解决这个问题，我们报告了对英国儿童急性淋巴细胞白血病随机试验 2003 年（UKALL 2003）所有 75 例 IRM 病例的分析。IRM 的 5 年累积发生率为 2.4%（95%置信区间[CI]，1.9%-3.0%），占 249 例试验死亡病例的 75 例（30%）和 117 例 TRM 死亡病例的 75 例（64%）。IRM 占 TRM 的比例在诱导期大于其他阶段（77%比 56%；P=0.02）。68%的病例与细菌感染相关（64%为革兰氏阴性菌），20%与真菌感染相关。唐氏综合征是 IRM 的最重要危险因素（比值比[OR]，12.08；95%CI，6.54-22.32；P<0.0001）。此外，女孩发生 IRM 的风险呈上升趋势（OR，1.63；95%CI，1.02-2.61；P=0.04），且治疗强度也呈上升趋势（方案 B 与 A：OR，2.11[95%CI，1.24-3.60]；方案 C 与 A：OR，1.41[95%CI，0.76-2.62]；P=0.02）。重要的是，唐氏综合征患者在维持治疗期间发生 IRM 的风险显著更高（P=0.048）。我们的研究结果证实唐氏综合征是 IRM 的主要危险因素。高危患者群体和风险增加期应加强支持性治疗和预防性抗生素治疗。本研究在 Controlled-Trials.com 注册，编号为#ISRCTN07355119。
