Malignant neoplasms subsequent to treatment of inflammatory bowel disease with 6-mercaptopurine

OBJECTIVE: Most complications of 6-mercaptopurine (6MP) used in the treatme nt of inflammatory bowel disease (IBD) occur early, whereas neoplasms occur late in the course. Concern persists that the risk is increased when 6MP i s used. We report our experience with malignant tumors developing over 27 y r of treating IBD patients with 6MP. METHODS: A total of 591 patients with LED treated with 6MP; between 1969 an d 1997 were followed or traced until present to identify all malignant tumo rs and blood dyscrasias that had developed to determine the type, distribut ion, and duration of the LED, the dose and duration of 6MP therapy, the con current versus previous use of 6MP, the incidence and probable relationship of 6MP to specific neoplasms, and whether the 6MP had been effective in tr eatment. RESULTS: A total of 550 patients (93%) fulfilled the criteria for follow-up ; these included 380 with Crohn's disease (CD) and 170 with ulcerative coli tis (UC). Twenty-five patients had developed neoplasms (16 of 380 CD and ni ne of 170 UC) (p = 0.66). In half of the cases, the goal of therapy had bee n achieved with 6MP. In 10 patients, the neoplasm was diagnosed while the p atients were taking 6MP (40%) and in 15, many years after the 6MP had been terminated (60%). The incidence of neoplasms (25 of 550) was 2.7/1000 patie nt-years of follow-up. The most common neoplasms were found in the bowel (e ight of 550, 1.6%?; five CD, and three UC), and breast (three, 0.5%; two CD , and one UC). Non-Hodegkins lymphomas occurred in tu po patients with CD; one was cerebral and the other abdominal. One patient with CD developed Leu kemia. The duration of 6MP therapy ranged from 5 months to 22 yr, with a me an of 5 yr. The dose of 6MP ranged from a quarter of a tablet/day (12.5 mg) to 100 mg/day, with the majority in a range from 50 to 75 mg/day. CONCLUSION: In no instance could a neoplasm be attributed to the use of 6MP . The incidence of colon cancer is not greater than that with long standing colitis. Suspicion of a relationship between 6MP and leukemia/lymphoma per sists, but the incidence is low. This must be weighed against the improved quality of life due to 6MP for patients with IBD. (C) 1999 by Am. Cell. of Gastroenterology.