Abstract
High-dose methotrexate (HD-MTX) courses with concurrent oral low-dose MTX/6-mercaptopurine (6MP) for childhood acute lymphoblastic leukaemia (ALL) are often followed by neutro- and thrombocytopenia necessitating treatment interruptions. Plasma MTX during HD-MTX therapy guides folinic acid rescue to prevent toxicities, but myelosuppression can also be prevented by pre-HD-MTX 6MP dose reductions. Accordingly, we monitored pre-HD-MTX erythrocyte levels of methylated 6MP metabolites (Ery-MeMP) and of thioguanine nucleotides (Ery-6TGN) as well as DNA-incorporated thioguanine nucleotides (DNA-TGN) in circulating leucocytes to identify patients at highest risk of post-HD-MTX myelosuppression. In multiple linear regression analyses of neutrophil and thrombocyte nadir values (adjusted for gender, age, risk group and 6MP dose) after 48 HD-MTX courses in 17 childhood ALL patients on MTX/6MP maintenance therapy, the pre-HD-MTX DNA-TGN levels in neutrophils (P < 0.0001), Ery-MeMP (P < 0.0001) and Ery-6TGN (P = 0.01) levels were significant predictors of post-HD-MTX neutrophil nadirs, whereas Ery-MeMP (P < 0.0001) was the only predictor of post-HD-MTX thrombocyte nadir. In conclusion, pre-HD-MTX 6MP metabolite levels may be applicable for 6M...Continue Reading
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Citations
Feb 16, 2016·European Journal of Medical Genetics·Kjeld Schmiegelow
Oct 21, 2016·Pediatric Blood & Cancer·Kjeld SchmiegelowSusanne Rosthoej
Apr 20, 2017·Pediatric Blood & Cancer·Linea Natalie ToksvangKjeld Schmiegelow
Nov 20, 2016·Journal of Gastroenterology and Hepatology·Berrie MeijerNanne K H de Boer
Oct 1, 2019·Therapeutic Drug Monitoring·Claire E Knezevic, William Clarke
Oct 7, 2017·European Journal of Haematology·Morten TulstrupKjeld Schmiegelow
Oct 28, 2016·Cancer Chemotherapy and Pharmacology·Stine Nygaard NielsenKjeld Schmiegelow
Nov 19, 2020·Pediatric Hematology and Oncology·Karin DreisigKjeld Schmiegelow