Abstract
Pharmacokinetic parameters of intracellular Ara-CTP were investigated in 65 children with leukemia (50 ALL, 15 AML). Separated peripheral or bone marrow blast cells were incubated for one hour in Ara-C containing medium (1 or 3 μg/ml) followed by reincubation in Ara -C free medium for three hours to determine the intracellular formation and retention of Ara-CTP.
The Ara-CTP retention showed marked differences in the morphologically classified groups at the time of initial diagnosis: non-T-ALL 67±25% (x±SD, n = 33), T-ALL 37±15% (n = 8) and AML 34±18% (n = 14). The difference between AML (p < 0.0006) as well as T-ALL p < 0.002 and non-T-ALL was significant.
The maximal accumulation of Ara-CTP (after 1h incub.), however, was not significantly different between AML, T-ALL, non-T-ALL and blast cells from children in relapse.
The similar cellular accumulation (Cmax, 1h Ara-C incubation) of Ara-CTP in all groups with a significantly more rapid decrease (3h without Ara-C) in T-ALL and AML represents a pharmacokinetic rationale for continuous Ara-C infusion in these subgroups as an alternative to the intensification by HD-Ara-C schedules.
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© 1996 Springer-Verlag Berlin Heidelberg
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Boos, J., Schiller, M., Pröbsting, B., Creutzig, U., Ritter, J. (1996). Intracellular Retention of Cytosine-Arabinoside-Triphosphate in Leukemic Blast Cells from Children. In: Hiddemann, W., et al. Acute Leukemias V. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 37. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78907-6_7
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DOI: https://doi.org/10.1007/978-3-642-78907-6_7
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