Summary
In the present study of 12 boys and 19 girls 2–16 years of age (median, 7 years) on oral 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy (MT) for non-B-cell acute lymphoblastic leukemia (ALL), we found that (a) during MT, 6-thioguanine nucleotides (6TGN) (the major cytotoxic metabolite of 6MP) accumulate in the erythrocytes (E-6TGN); (b) for patients receiving an unchanged dose of 6MP, no significant correlation could be demonstrated between the mean E-6TGN (mE-6TGN) and the dose of 6MP (r = −0.11,P = 0.28) (31 patients); (c) among 21 patients receiving 50–75 mg/m2 6MP, a variation of up to 3 orders of magnitude in mE-6TGN could be demonstrated, with the interindividual coefficient of variation (CV) in mE-6TGN for these patients being 0.31; (d) the median intraindividual CV in E-6TGN at an unchanged dose of 6MP was 0.11 (range, 0.04–0.18); and (e) the degree of myelodepression as measured by the mean white cell count was related to mE-6TGN (r = −0.55,P = 0.0006). These results indicate that E-6TGN could be a useful parameter for monitoring 6MP maintenance chemotherapy, although this needs to be explored in prospective studies.
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Abbreviations
- ALL:
-
acute lymphoblastic leukemia
- E-MTX:
-
erythrocyte concentration of methotrexate
- E-6TGN:
-
erythrocyte concentration of 6-thioguanine nucleotides
- mE-6TGN:
-
mean E-6TGN
- mWBC:
-
mean white cell count
- 6MP:
-
6-mercaptopurine
- MT:
-
maintenance chemotherapy
- MTX:
-
methotrexate
- MTXpg:
-
methotrexate polyglutamates
- WBC:
-
white cell count
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Schmiegelow, K., Bruunshuus, I. 6-Thioguanine nucleotide accumulation in red blood cells during maintenance chemotherapy for childhood acute lymphoblastic leukemia, and its relation to leukopenia. Cancer Chemother Pharmacol 26, 288–292 (1990). https://doi.org/10.1007/BF02897232
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DOI: https://doi.org/10.1007/BF02897232