BONE-MARROW TOXICITY CAUSED BY AZATHIOPRINE IN INFLAMMATORY BOWEL-DISEASE - 27 YEARS OF EXPERIENCE

Myelosuppression is an important and potentially lethal complication o f azathioprine treatment. The blood count has been reviewed in all pat ients treated with azathioprine for inflammatory bowel disease over 27 years in one hospital. Altogether 739 patients (422 with Crohn's dise ase, 284 with ulcerative colitis, and 33 with indeterminate colitis) w ere treated with 2 mg/kg/day azathioprine for a median of 12 . 5 month s (range 0 . 5-132) between 1964 and 1991. Full blood counts were perf ormed monthly for the duration of treatment. In 37 patients (5%) who d eveloped bone marrow toxicity, the drug was withdrawn or the dose redu ced. Thirty two of these patients were asymptomatic and five developed symptoms. Leucopenia (white blood count less than 3.0X10g/l) occurred in 28 (3-8%) patients, in nine of whom it was severe (white blood cou nt <2.0X10(9)/l). Of these nine patients, three were pancytopenic: two died from sepsis and the other had pneumonia but recovered. A further two patients with severe leucopenia developed a mild upper respirator y infection only. Thrombocytopenia (platelet count < 100 000 x 10(6)/l ) in 15 patients was associated with leucopenia in six and developed i n isolation in a further nine (total 2%). Isolated thrombocytopenia wa s never clinically severe. Myelotoxicity from azathioprine developed a t any time during drug treatment (range 2 weeks-11 years after startin g the drug) and occurred either suddenly or over several months. Bone marrow suppression as a result of azathioprine treatment is uncommon w hen a moderate dose is used, but is potentially severe. Leucopenia is the commonest and most important haematological complication. Regular monitoring of the full blood count is recommended during treatment.