Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
Infect Agent Cancer. 2013 Dec 2;8(1):47. doi: 10.1186/1750-9378-8-47.
Children with Down syndrome (DS) are at high risk of infectious toxicity when treated with acute lymphoblastic leukemia chemotherapy protocols optimized in children without DS. Our objective was to determine if children with DS and acute myeloid leukemia (AML) have a different risk of infection when treated with chemotherapy protocols developed for children with DS compared to AML treatment protocols developed for children without DS.
We conducted a retrospective, population-based cohort study that included DS children ≤ 18 years of age with de novo, non-M3 AML diagnosed between January 1995 and December 2004, and treated at 15 Canadian centers. Patients were monitored for infection from initiation of AML treatment until recovery from the last cycle of chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse, persistent disease or death (whichever occurred first). Trained research associates abstracted all information from each site.
There were 31 children with DS included; median age was 1.7 (range 0.1-11.1) years. Eleven were treated according to a DS-specific protocol while 20 were treated with non-DS specific protocols. A total of 157 courses of chemotherapy were delivered. Microbiologically documented sterile site infection occurred in 11.9% and 14.3% of DS-specific and non-DS specific AML treatment courses respectively. Sepsis was rare and there were no infection-related deaths. In multiple regression, treatment with a DS-specific protocol was independently associated with a reduction in microbiologically documented sterile site infection (adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.42-0.99; P = 0.044), and clinically documented infection (adjusted OR 0.36, 95% CI 0.14-0.91; P = 0.031) but not bacteremia (adjusted OR 0.73, 95% CI 0.44-1.22; P = 0.231).
Our study suggests that children with DS do not experience excessive infectious toxicity during treatment for AML compared to children without DS. Incorporation of DS-specific AML treatment protocols is associated with a more favorable infection profile for children with DS-AML.
患有唐氏综合征（DS）的儿童在接受针对无 DS 儿童优化的急性淋巴细胞白血病化疗方案治疗时，具有发生传染性毒性的高风险。我们的目标是确定患有 DS 和急性髓系白血病（AML）的儿童在接受针对 DS 儿童制定的化疗方案治疗时，与针对无 DS 儿童制定的 AML 治疗方案相比，感染风险是否不同。
我们进行了一项回顾性、基于人群的队列研究，纳入了 1995 年 1 月至 2004 年 12 月期间在加拿大 15 个中心诊断为新发非 M3 AML 的≤18 岁 DS 儿童患者。从 AML 治疗开始至最后一个化疗周期、造血干细胞移植预处理、复发、持续疾病或死亡（以先发生者为准），对患者进行感染监测。经过培训的研究助理从每个研究中心提取所有信息。
共纳入 31 名 DS 儿童患者，中位年龄为 1.7 岁（范围为 0.1-11.1 岁）。其中 11 名患者接受了 DS 特异性方案治疗，20 名患者接受了非 DS 特异性方案治疗。共进行了 157 个化疗疗程。DS 特异性方案治疗组和非 DS 特异性 AML 治疗组分别有 11.9%和 14.3%的患者发生微生物学证实的无菌部位感染。败血症很少见，无感染相关死亡。多因素回归分析显示，采用 DS 特异性方案治疗与微生物学证实的无菌部位感染（校正优势比（OR）0.65，95%置信区间（CI）0.42-0.99；P=0.044）和临床证实的感染（校正 OR 0.36，95%CI 0.14-0.91；P=0.031）显著降低相关，但与菌血症（校正 OR 0.73，95%CI 0.44-1.22；P=0.231）无关。
与无 DS 儿童相比，DS 儿童在接受 AML 治疗时并未经历过度的传染性毒性。采用 DS 特异性 AML 治疗方案与 DS-AML 患者更有利的感染谱相关。
