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Low-dose 6-mercaptopurine in inflammatory bowel disease is associated with minimal hematologic toxicity
C N Bernstein1, L Artinian, P A Anton
1Department of Medicine, University of California, Los Angeles.
Abstract:
A feared complication of therapy with 6-mercaptopurine (6-MP) is myelosuppression. To evaluate whether rigorous blood count monitoring is necessary, we prospectively followed the hematologic profiles of 57 patients with inflammatory bowel disease who were treated with low-dose 6-MP. Most patients (97%) were treated initially with a single dose of 50 mg/day and 79% never used more than 50 mg/day. Blood counts were obtained at weekly intervals over the first month, every two weeks for the second month, and monthly thereafter in the first year. Sixteen (28%) developed mild leukopenia (white blood count < 4.5 x 10(3)/mm3). No patient had a white blood cell count < 2.8 x 10(3)/mm3 and no patient developed leukopenia prior to three months of treatment. In only five patients did the leukopenia prompt a change in 6-mercaptopurine dose. Very mild thrombocytopenia (platelet count of < 145 x 10(3)/mm3) developed in three (5%) and macrocytosis (mean cell volume > 101 fl) was seen in nine (16%). In conclusion, leukopenia was not uncommon in patients treated with low-dose 6-MP, but was not clinically significant. Leukopenia occurred no earlier than three months and as late as 42 months into therapy. Thrombocytopenia was uncommon, mild, and was not associated with apparent bleeding. Macrocytosis may occur in the absence of vitamin B12 and folate deficiencies. Patients can be spared from weekly blood count monitoring when using low-dose 6-mercaptopurine treatment.
Insights
Low-dose 6-mercaptopurine (6-MP) for inflammatory bowel disease rarely causes significant myelosuppression. Patients treated with 6-MP can avoid frequent blood count monitoring due to mild and infrequent hematologic changes.
Area of Science:
- Gastroenterology
- Pharmacology
- Hematology
Background:
- Myelosuppression is a feared complication of 6-mercaptopurine (6-MP) therapy.
- The necessity of rigorous blood count monitoring during 6-MP treatment remains a concern for patients with inflammatory bowel disease (IBD).
Purpose of the Study:
- To evaluate the necessity of rigorous blood count monitoring in patients with IBD treated with low-dose 6-mercaptopurine.
- To assess the incidence and clinical significance of hematologic changes, including myelosuppression, during low-dose 6-MP therapy.
Main Methods:
- Prospective follow-up of hematologic profiles in 57 IBD patients treated with low-dose 6-MP.
- Blood counts were monitored at weekly, bi-weekly, and monthly intervals over the first year of treatment.
Main Results:
- Mild leukopenia (28%) and macrocytosis (16%) were observed, but were not clinically significant.
- Thrombocytopenia was uncommon (5%), mild, and not associated with bleeding.
- Leukopenia occurred no earlier than three months and as late as 42 months into therapy, with dose changes in only five patients.
Conclusions:
- Low-dose 6-mercaptopurine treatment for IBD is associated with infrequent and mild hematologic changes.
- Rigorous weekly blood count monitoring may not be necessary for patients on low-dose 6-MP, potentially reducing patient burden.
- The study suggests that patients can be spared from frequent blood count monitoring when using low-dose 6-mercaptopurine treatment.