Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia

Cancer Chemotherapy and Pharmacology
Sophia Ingeborg VangJacob Nersting

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

References

Jan 1, 1996·Cancer Chemotherapy and Pharmacology·F InnocentiM Del Tacca
Sep 23, 2006·Leukemia·T V Ch SkärbyUNKNOWN Nordic Society of Paediatric Haematology and Oncology (NOPHO)
Dec 17, 2009·Leukemia·K SchmiegelowUNKNOWN Nordic Society of Paediatric Haematology and Oncology
Dec 20, 2011·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Jack H JacobsenJacob Nersting
Jun 18, 2014·Journal of Pediatric Hematology/oncology·Kjeld SchmiegelowJacob Nersting

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Citations

Feb 16, 2016·European Journal of Medical Genetics·Kjeld 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 28, 2016·Cancer Chemotherapy and Pharmacology·Stine Nygaard NielsenKjeld Schmiegelow

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