Khan Nabeel, Patel Dhruvan, Trivedi Chinmay, Kavani Himanshu, Pernes Tyler, Medvedeva Elina, Lewis James, Xie Dawei, Yang Yu-Xiao
1Department of Gastroenterology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA; 2Division of Gastroenterology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA; 3Department of Internal Medicine, St. Mary Medical Center, Langhorne, Pennsylvania, USA; 4Center of Clinical Epidemiology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA; 5Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Am J Gastroenterol. 2021 Apr;116(4):741-747. doi: 10.14309/ajg.0000000000001058.
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are rare myeloid clonal disorders that commonly affect the elderly population and have poor prognosis. There are limited data on the risk of AML/MDS among patients with inflammatory bowel disease (IBD), especially on the impact of thiopurines (TPs).
We conducted a retrospective cohort study among patients with IBD from Veteran Affairs data set. The exposure of interest was TP exposure: (i) never exposed to TPs, (ii) past TP use (discontinued >6 months ago), (iii) current TP use with a cumulative exposure of <2 years, and (iv) current TP use with a cumulative exposure of ≥2 years. The outcome of interest was a composite outcome of incident diagnosis of AML and/or MDS. Cox regression was used to estimate the adjusted and unadjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for AML/MDS risk associated with TP use defined as a time-varying exposure.
Among 56,314 study patients, 107 developed AML/MDS. The overall incidence of AML/MDS in the IBD population was 18.7 per 100,000 patient-years. The incidences among those never exposed to TPs, past users of TPs, current users of TPs with a cumulative exposure of <2 years, and current users of TPs with a cumulative exposure of ≥2 years were 17.0, 17.7, 30.4, and 30.3 per 100,000 patient-years, respectively. In multivariable Cox regression analysis, compared with never exposed to TPs, current use of TPs was associated with increased risk (adjusted HR 3.05; 95% CI 1.54-6.06, P = 0.0014 for current use of TPs with a cumulative exposure of <2 years and adjusted HR 2.32; 95% CI 1.22-4.41, P = 0.0101 for current use of TPs with a cumulative exposure of ≥2 years), whereas past TP exposure was not.
Among patients with IBD, current TP use was associated with an increased risk of AML/MDS, which reverts to baseline after discontinuation of TP use.
急性髓系白血病（AML）和骨髓增生异常综合征（MDS）是罕见的髓系克隆性疾病，通常影响老年人群，预后较差。关于炎症性肠病（IBD）患者发生AML/MDS的风险的数据有限，尤其是硫唑嘌呤（TPs）的影响。
我们对退伍军人事务数据集的IBD患者进行了一项回顾性队列研究。感兴趣的暴露因素是TP暴露：（i）从未暴露于TPs，（ii）既往使用过TPs（停用超过6个月），（iii）当前使用TPs且累积暴露时间小于2年，以及（iv）当前使用TPs且累积暴露时间≥2年。感兴趣的结局是AML和/或MDS的新发诊断的复合结局。Cox回归用于估计与定义为随时间变化的暴露的TP使用相关的AML/MDS风险的调整和未调整风险比（HRs）及95%置信区间（CIs）。
在56314例研究患者中，107例发生了AML/MDS。IBD人群中AML/MDS的总体发病率为每100000患者年18.7例。从未暴露于TPs者、既往TP使用者、当前累积暴露时间小于2年的TP使用者以及当前累积暴露时间≥2年的TP使用者中，发病率分别为每100000患者年17.0例、17.7例、30.4例和30.3例。在多变量Cox回归分析中，与从未暴露于TPs相比，当前使用TPs与风险增加相关（累积暴露时间小于2年的当前TP使用者的调整HR为3.05；95%CI为1.54 - 6.06，P = 0.0014；累积暴露时间≥2年的当前TP使用者的调整HR为2.32；95%CI为1.22 - 4.41，P = 0.0101），而既往TP暴露则不然。
在IBD患者中，当前使用TPs与AML/MDS风险增加相关，停用TPs后风险恢复至基线水平。
