Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia
Research output: Contribution to journal › Journal article › Research › peer-review
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 6MP dose adjustments to prevent HD-MTX-induced myelosuppression.
Original language | English |
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Journal | Cancer Chemotherapy and Pharmacology |
Volume | 75 |
Issue number | 5 |
Pages (from-to) | 1089-1093 |
Number of pages | 5 |
ISSN | 0344-5704 |
DOIs | |
Publication status | Published - May 2015 |
- 6-Mercaptopurine, Adolescent, Antineoplastic Combined Chemotherapy Protocols, Bone Marrow, Child, Child, Preschool, Dose-Response Relationship, Drug, Drug Administration Schedule, Erythrocytes, Female, Guanine Nucleotides, Humans, Infant, Male, Methotrexate, Neutropenia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Thionucleotides, Thrombocytopenia
Research areas
ID: 161270580