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6‐methylmercaptopurine‐induced leukocytopenia during thiopurine therapy in inflammatory bowel disease patients
Author(s) -
Meijer Berrie,
Kreijne Joany E,
Moorsel Sofia A W,
Derijks Luc J J,
Bouma Gerd,
Mulder Chris J J,
Wong Dennis R,
Woude C Janneke,
Bodegraven Adriaan A,
Boer Nanne K H
Publication year - 2017
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.13656
Subject(s) - leukocytopenia , medicine , thiopurine methyltransferase , gastroenterology , inflammatory bowel disease , adverse effect , white blood cell , interquartile range , regimen , surgery , chemotherapy , disease
Background and Aim Thiopurines have a favorable benefit–risk ratio in the treatment of inflammatory bowel disease. A feared adverse event of thiopurine therapy is myelotoxicity, mostly occurring due to toxic concentrations of the pharmacologically active metabolites 6‐thioguaninenucleotides. In oncology, myelosuppression has also been associated with elevated 6‐methylmercaptopurine (6‐MMP). In this case series, we provide a detailed overview of 6‐MMP‐induced myelotoxicity in inflammatory bowel disease patients. Methods We retrospectively scrutinized pharmacological laboratory databases of five participating centers over a 5‐year period. Patients with leukocytopenia at time of elevated 6‐MMP levels (>5700 pmol/8 × 10 8 red blood cells) were included for detailed chart review. Results In this case series, we describe demographic, clinical, and pharmacological aspects of 24 cases of 6‐MMP‐induced myelotoxicity on weight‐based thiopurine therapy with a median steady‐state 6‐MMP level of 14 500 pmol/8 × 10 8 red blood cells (range 6600–48 000). All patients developed leukocytopenia (white blood cell count 2.7 ± 0.9 × 10 9 /L) after a median period of 11 weeks after initiation of thiopurine therapy (interquartile range 6–46 weeks). Eighteen patients (75%) developed concurrent anemia (median hemoglobin concentration 6.9 × 10 9 /L), and four patients developed concurrent thrombocytopenia (median platelet count 104 × 10 9 /L). Leukocytopenia resolved in 20 patients (83%) within 4 weeks upon altered thiopurine treatment regimen, and white blood cell count was increasing, but not yet normalized, in the remaining four patients. Conclusion We observed that thiopurine‐induced myelotoxicity also occurs because of (extremely) high 6‐MMP concentrations in patients with a skewed thiopurine metabolism. Continued treatment with adapted thiopurine therapy was successful in almost all patients.