How should mercaptopurine dosing be adjusted in a patient with TPMT deficiency?

• A. Reduce the mercaptopurine dose or avoid it, with more frequent CBC monitoring guided by TPMT testing.
• B. Double the dose if TPMT activity is low.
• C. Cease all chemotherapy permanently.
• D. Do not adjust dose and monitor only monthly.

Answer: (A)

TPMT deficiency means the body cannot efficiently inactivate mercaptopurine, so more of the active drug and its cytotoxic metabolites accumulate in the bone marrow. That raises the risk of serious myelosuppression. The appropriate approach is to substantially lower the mercaptopurine dose or avoid it, with more frequent CBC monitoring to catch marrow suppression early. TPMT testing guides how much adjustment is needed; if activity is very low or absent, dose reduction is substantial or alternative therapy may be considered. Doubling the dose would increase toxicity, while not adjusting the dose or monitoring monthly would miss early signs of marrow suppression.