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Clin Gastroenterol Hepatol. 2009 Nov;7(11):1195-201; quiz 1141-2. doi: 10.1016/j.cgh.2009.07.019. Epub 2009 Jul 22.

Timing of myelosuppression during thiopurine therapy for inflammatory bowel disease: implications for monitoring recommendations.

Author information

1
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6021, USA. lewisjd@mail.med.upenn.edu

Abstract

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

PMID:
19631285
PMCID:
PMC4435979
DOI:
10.1016/j.cgh.2009.07.019
[Indexed for MEDLINE]
Free PMC Article

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