Abstract |
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.
|
Authors | J B Andersen, C Szumlanski, R M Weinshilboum, K Schmiegelow |
Journal | Acta paediatrica (Oslo, Norway : 1992)
(Acta Paediatr)
Vol. 87
Issue 1
Pg. 108-11
(Jan 1998)
ISSN: 0803-5253 [Print] Norway |
PMID | 9510461
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Mercaptopurine
- Methyltransferases
- thiopurine methyltransferase
- Methotrexate
|
Topics |
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage, adverse effects, pharmacokinetics)
- Child
- Child, Preschool
- Dose-Response Relationship, Drug
- Drug Interactions
- Follow-Up Studies
- Humans
- Male
- Mercaptopurine
(administration & dosage)
- Methotrexate
(administration & dosage)
- Methyltransferases
(deficiency)
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
(complications, diagnosis, drug therapy)
|