Why is TPMT testing important before starting 6‑mercaptopurine in pediatric oncology?

• A. TPMT deficiency increases risk of severe myelosuppression with standard 6‑MP dosing; test TPMT activity/genotype and adjust dose accordingly or avoid.
• B. TPMT deficiency reduces risk of nephrotoxicity and allows higher dosing.
• C. TPMT status only affects hepatic toxicity with 6‑MP.
• D. TPMT status has no clinical relevance for 6‑MP therapy.

Answer: (B)

TPMT is the enzyme that inactivates thiopurines like 6-mercaptopurine. When TPMT activity is low due to genetic variants, the drug isn’t inactivated as well, leading to higher levels of active metabolites that can strongly suppress the bone marrow. That makes severe myelosuppression a real danger if standard 6-MP doses are used. Testing TPMT activity or genotype before starting therapy lets you tailor the dose: with normal activity you can proceed with standard dosing, with reduced activity you start with a lower dose and monitor closely (often adjusting more gradually), and with little or no activity you may need to avoid 6-MP or use significant dose reductions and alternative strategies. This approach prevents dangerous cytopenias while still aiming for treatment efficacy.