6-Mercaptopurine metabolic profiles and clinical outcomes in TPMT and NUDT15 phenotypes during maintenance therapy for Thai paediatric acute lymphoblastic leukaemia

Prospective cohort of 104 ALL children during maintenance phase, TPMT/NUDT15 genotyping, 6-MP metabolite measurement (6-TGN, 6-MMPN), correlation with toxicities (early neutropenia, hepatotoxicity) and tolerated dose by phenotypic group

104 Thai ALL children during maintenance therapy are prospectively followed for 5 months with TPMT/NUDT15 genotyping and monthly 6-MP metabolite measurement (6-TGN, 6-MMPN). NM/PM patients (normal TPMT, NUDT15-deficient) have the lowest tolerated 6-MP doses (18 mg/m²) while the IM/IM group has the highest early neutropenia rate (75%). TPMT variants cause 6-TGN accumulation (myelosuppression), while NUDT15 variants lower 6-TGN and raise 6-MMPN (hepatotoxicity). These data validate the interest of combined TPMT+NUDT15 phenotyping for 6-MP toxicity monitoring in Asian populations.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

NUDT15 is the primary determinant of thiopurine toxicity in Asian populations (much higher prevalence of NUDT15 variants than in Europe), and the TPMT+NUDT15 combination is particularly informative. These Thai data reinforce CPIC recommendations for systematic NUDT15 testing before 6-MP initiation in Asian populations, with impact on initial doses and metabolite monitoring.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 1/2 · Sample size: 0/1 · Publication status: 1/1 → Total: 6/10