The role of leukopenia in the 6-mercaptopurine-induced remission of refractory Crohn's disease

Abstract

Objectives: 1) to determine the frequency of induced leukopenia in patients with refractory Crohn's disease treated with 6-Mercaptopurine (6-MP). 2) to determine the influence of 6-MP-induced leukopenia on achieving remission [including the three major specific goals of therapy: (a) elimination or reduction of steroids, (b) healing of abscesses and fistulas, and (c) elimination of recurrent intestinal obstruction] and the effect on the rate and percentage of improvement in the CCFA-IOIBD index of Crohn's disease activity after 3 months of 6-MP therapy. 3) to determine whether an improvement of leukopenia was accomplished by an increased risk of clinical bone marrow depression.

Methods: We reviewed the course of 98 consecutive patients with refractory Crohn's disease treated with 6-MP and compared the 51 who developed leukopenia and the 47 who did not, in regard to achievement of remission, length of time until remission, rate of recurrence, and time until recurrence.

Results: 1) The mean time to remission was 8.8 wk for patients with leukopenia versus 14.3 wk for those without leukopenia. 2) A strong positive correlation exists between 6-MP induced leukopenia and the achievement and maintenance of remission in refractory Crohn's disease. This was evident in the analysis of response in specific goals and in the activity index. 3) There was no clinical evidence of bone marrow suppression in the 51 patients who developed 6-MP induced leukopenia.

Conclusions: 1) Increasing the dose of 6-MP in patients with refractory Crohn's disease who have not yet responded and who have not achieved leukopenia will very likely increase the efficacy of this drug. 2) Influenced by the results of this study, we have launched a double-blind prospective study to evaluate the relationship between the induction of leukopenia with 6-MP and the achievement of remission.