Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6021, USA.
Clin Gastroenterol Hepatol. 2009 Nov;7(11):1195-201; quiz 1141-2. doi: 10.1016/j.cgh.2009.07.019. Epub 2009 Jul 22.
BACKGROUND & AIMS: Thiopurines (azathioprine and 6-mercaptopurine) can induce life-threatening myelosuppression. This study determined the frequency, timing, and outcomes of mild and severe myelosuppression after initiation of thiopurine therapy.
This retrospective cohort study included patients with inflammatory bowel disease who were new users of thiopurines; those tested for thiopurine methyltransferase levels before therapy were excluded. Patients were followed from their first thiopurine prescription until the earliest of severe leukopenia (white blood cell count, <1.0 x 10(9)/L), severe thrombocytopenia (platelet level, <20 x 10(9)/L), the end of therapy, the first gap in therapy, disenrollment, or December 31, 2006.
Among 1997 new users, the incidence of severe leukopenia per 100 person-months was 0.16 (95% confidence interval [CI], 0.03-0.29; n = 6) in weeks 0 to 8, 0.00 in weeks 9 to 24, and 0.01 (95% CI, 0-0.03; n = 3) after week 26 of therapy. The incidence of severe neutropenia and severe thrombocytopenia per 100 person-months during the first 8 weeks of therapy was 0.51 (95% CI, 0.31-0.80; n = 19) and 0.08 (95% CI, 0.02-0.23; n = 3), respectively. During the first 8 weeks, the median duration from a normal white blood cell count to severe leukopenia was 13 days (range, 8-26 d) and to severe neutropenia was 14 days (range, 7-23 d).
The high incidence of severe myelosuppression justifies frequent monitoring during the first 8 weeks of therapy. Subsequently, the rate of severe myelosuppression and the proportion of patients who progress from mild to severe myelosuppression decrease, justifying less-frequent monitoring.
硫唑嘌呤（巯嘌呤和 6-巯基嘌呤）可引起危及生命的骨髓抑制。本研究旨在确定硫嘌呤治疗开始后轻度和重度骨髓抑制的发生频率、时间和结局。
本回顾性队列研究纳入了新使用硫嘌呤的炎症性肠病患者；排除了在治疗前检测硫嘌呤甲基转移酶水平的患者。患者从首次使用硫嘌呤处方开始随访，直至出现严重白细胞减少症（白细胞计数<1.0×10(9)/L）、严重血小板减少症（血小板计数<20×10(9)/L）、治疗结束、治疗首次中断、退出或 2006 年 12 月 31 日。
在 1997 名新使用者中，每 100 人-月重度白细胞减少症的发生率在治疗第 0 至 8 周为 0.16（95%置信区间[CI]，0.03-0.29；n=6），第 9 至 24 周为 0.00，第 26 周后为 0.01（95%CI，0-0.03；n=3）。在治疗的前 8 周内，每 100 人-月重度中性粒细胞减少症和重度血小板减少症的发生率分别为 0.51（95%CI，0.31-0.80；n=19）和 0.08（95%CI，0.02-0.23；n=3）。在前 8 周内，从白细胞计数正常到重度白细胞减少症的中位时间为 13 天（范围，8-26 d），从白细胞计数正常到重度中性粒细胞减少症的中位时间为 14 天（范围，7-23 d）。
重度骨髓抑制的高发生率证明了在治疗的前 8 周内应频繁监测。随后，重度骨髓抑制的发生率和从轻度骨髓抑制进展为重度骨髓抑制的患者比例下降，证明监测频率可以降低。
