TY - JOUR
T1 - Pharmacokinetics, dose adjustments, and 6-mercaptopurine/ methotrexate drug interactions in two patients with thiopurine methyltransferase deficiency
AU - Brandt Andersen, J.
AU - Szumlanski, C.
AU - Weinshilboum, R. M.
AU - Schmiegelow, K.
PY - 1998
Y1 - 1998
N2 - Two children with acute lymphoblastic leukaemia (ALL) were found to be thiopurine methyltransferase (TPMT)-deficient by both genotype and phenotype. They were monitored with haematological parameters and red blood cell concentrations of 6-thioguanine nucleotides (E-6TGN) and methotrexate (E- MTX, including MTX polyglutamates), in relation to the doses of 6- mercaptopurine (6MP) and methotrexate (MTX), during their maintenance chemotherapy. Both patients developed severe pancytopenia at the standard protocol dose of 6MP. Even at 25% and 5%, respectively, of the protocol dose of 6MP, they achieved E-6TGN values several-fold above the population median, but without unacceptable bone-marrow toxicity. Their high E-6TGN values had only a minor influence on their E-MTX values and their tolerance to oral MTX, but severe pancytopenia followed high-dose MTX infusions. Due to the risk of fatal myelosuppression we recommend up-front determination of TPMT activity in patients treated with 6MP or azathioprine.
AB - Two children with acute lymphoblastic leukaemia (ALL) were found to be thiopurine methyltransferase (TPMT)-deficient by both genotype and phenotype. They were monitored with haematological parameters and red blood cell concentrations of 6-thioguanine nucleotides (E-6TGN) and methotrexate (E- MTX, including MTX polyglutamates), in relation to the doses of 6- mercaptopurine (6MP) and methotrexate (MTX), during their maintenance chemotherapy. Both patients developed severe pancytopenia at the standard protocol dose of 6MP. Even at 25% and 5%, respectively, of the protocol dose of 6MP, they achieved E-6TGN values several-fold above the population median, but without unacceptable bone-marrow toxicity. Their high E-6TGN values had only a minor influence on their E-MTX values and their tolerance to oral MTX, but severe pancytopenia followed high-dose MTX infusions. Due to the risk of fatal myelosuppression we recommend up-front determination of TPMT activity in patients treated with 6MP or azathioprine.
KW - 6-mercaptopurine
KW - Acute lymphoblastic leukaemia
KW - Methotrexate
KW - Thiopurine methyltransferase deficiency
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U2 - 10.1080/08035259850158001
DO - 10.1080/08035259850158001
M3 - Article
C2 - 9510461
AN - SCOPUS:0031933720
SN - 0803-5253
VL - 87
SP - 108
EP - 111
JO - Acta Paediatrica, International Journal of Paediatrics
JF - Acta Paediatrica, International Journal of Paediatrics
IS - 1
ER -