Influence of thiopurine methyltransferase gene polymorphism on Egyptian children with acute lymphoblastic leukaemia.

Abstract

Thiopurine methyltransferase (TPMT) gene polymorphism regulates thiopurine therapeutic efficacy and toxicity. The aim of this study was to determine the influence of TPMT gene polymorphism in Egyptian children with acute lymphoblastic leukaemia (ALL). Sixty-four patients with ALL, T lineage (27%) and pre-B phenotype (73%), who were treated with BFM 90 or CCG 1991 standard risk protocol, and who also experiencedmyleosuppresion toxicity and required interruption and/ormodification of thiopurine chemotherapy were recruited over a year period. Thirty-two patients were on maintenance and another 32 completed their chemotherapy. Seventy healthy age-matched and sex-matched children served as controls. They were subjected to clinical assessment, haematological panel investigations and TPMT gene polymorphism for G238C, G460A and A719G alleles assessment using PCRfollowed byRFLP analysis.Although none of the studied patients had themutantTPMTvariant alleles,myelosuppression toxicity in the form of different degree of neutropenia was detected in all patients. As a result of myelosuppression toxicity, most of the patients needed 6-MP dose modification either once (53.1%), twice (15.6%), or ≥ thrice (25.1%) during their maintenance course and 96.9% of the patients required to stop 6-MP for less than a week (62.5%), up to 2 weeks (28.1%), or > 2 weeks (6.3%). Patients also developed infection who mostly (71%) needed hospitalization. None of the studied G238C, G460A and A719G TPMT variant alleles were detected. Infections and febrile neutropenia were common causes of 6-PM dose modification and interruption.