Thiopurine methyltransferase deficiency in childhood lymphoblastic leukaemia: 6-mercaptopurine dosage strategies

✍ Scribed by Lennard, Lynne; Lewis, Ian J.; Michelagnoli, Maria; Lilleyman, John S.

• Book ID: 101218960
• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 76 KB
• Volume: 29
• Category: Article
• ISSN: 0098-1532
• DOI: 10.1002/(sici)1096-911x(199710)29:4<252::aid-mpo3>3.0.co;2-l

✦ Synopsis

Daily 6-mercaptopurine (6MP) forms the backbone of continuing chemotherapy for childhood lymphoblastic leukaemia (ALL). A major metabolic route is catalysed by thiopurine methyltransferase (TPMT). TPMT deficiency occurs in 1 in 300 individuals and results in high concentrations of thioguanine nucleotides (TGNs), cytotoxic 6MP metabolites. A leukaemic child taking 6MP repeatedly developed profound pancytopenias. TPMT deficiency was confirmed. TGN formation was then studied on attenuated 6MP dosages. Four weekly oral doses of 75 mg/m 2 6MP produced TGNs of 2348 pmol/8 × 10 8 red cells, nearly double the maximum TGNs recorded in ALL children with TPMT activity taking long term daily 75 mg/m 2 6MP. Grossly elevated TGN concentrations were also produced at 10% standard 6MP dosage (7.5 mg/m 2 daily), accompanied by unacceptable 6MP toxicity (neutropenia, diarrhoea, vomiting). The child was eventually stabilised on 10% alternate day therapy and after 15 weeks TGNs were 1670 pmol, just above the upper end of the TGN range for ALL children with TPMT activity.