Phenotypic analysis of 1-B-D-arabinofuranosylcytosine deamination in patients treated with high doses and correlation with response.
Two phenotypes for 1-B-D-arabinofuranosylcytosine (ara-C) deamination corresponding to a ratio of distribution for "slow" (ratio, less than or equal to 14) vs "fast" (ratio, greater than 14) deaminators of 70%:30%, have been determined on the basis of studies on plasma ratios of 1-B-D-arabinofuranosyluracil/ara-C (ara-U/ara-C) in 56 subjects treated with high-dose ara-C (3 g/m2 infused i.v. over 3 h). A positive correlation of age with the concentration of ara-U was observed. In a subgroup of 36 patients with leukemia, the ara-U/ara-C pattern was similar to that observed for all 56 subjects. In these leukemic patients, who were treated with combinations of ara-C plus other conventional agents, a tendency toward a positive response (complete response + partial response) was found for those showing low ara-U/ara-C ratios (slow deaminators). The phenotypic effect of deamination in acute leukemia needs to be evaluated prospectively.
Kreis
W
W
Department of Medicine, North Shore University Hospital, Manhasset, New York 11030.
Lesser
M
M
Budman
D R
DR
Arlin
Z
Z
DeAngelis
L
L
Baskind
P
P
Feldman
E J
EJ
Akerman
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001086:Arabinofuranosyluracil / Q000097:blood; D003561:Cytarabine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D003641:Deamination; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012737:Sex Factors
D003561:Cytarabine; D012710:Serum Albumin, Bovine; D001086:Arabinofuranosyluracil