6-Thioguanine nucleotide accumulation in red blood cells during maintenance chemotherapy for childhood acute lymphoblastic leukemia, and its relation to leukopenia.
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.
Schmiegelow
K
K
Department of Pediatrics, University Hospital, Copenhagen, Denemark.
Bruunshuus
I
I
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006150:Guanine Nucleotides / Q000097:blood*; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008991:Monitoring, Physiologic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D013873:Thionucleotides / Q000097:blood*
D006150:Guanine Nucleotides; D013873:Thionucleotides; C003964:6-thioguanylic acid; D015122:Mercaptopurine; D008727:Methotrexate