Abstract | BACKGROUND: PATIENTS AND METHODS: At the time of diagnosis, peripheral or bone marrow blast cells from 41 children with ALL and 13 with relapsed ALL were incubated in Ara-C containing medium (1 hour, 1 or 3 micrograms/ml) followed by reincubation in Ara-C free medium (3 h). Intracellular Ara CTP formation and Ara-CTP retention were determined. MAIN RESULTS:
Ara-CTP formation did not show marked differences between the different immunological subtypes. Ara-CTP retention, however, was significantly lower in T-ALL (37 +/- 15%, n = 8) compared to non- T-ALL (67 +/- 25%, n = 33; p < 0.003). Ara-CTP retention was also significantly different in children with and without persistence of peripheral blast cells after one week of prednison treatment (71 +/- 30%, n = 9 and 53 +/- 19%, n = 21; p = 0.031) as well as in children with and without complete bone marrow remission on day 15 of the ALL-BFM treatment protocol (66 +/- 17%, n = 19 and 43 +/- 18%, n = 11; p = 0.018). Ara-CTP retention was inversely correlated with the risk groups defined by the ALL-BFM treatment protocols (standard 79 +/- 29, intermediate 59 +/- 25, high risk 47 +/- 21%). A trend towards lower Ara-CTP retention was observed in relapsed leukemias (relapsed non- T-ALL 51 +/- 17%, p = 0.061). The difference in the probability of event free survival (following risk group adapted treatment according to ALL-BFM trials) between children with high (> or = 72%; 0.92 +/- 0.08) and low (< 72%: 0.58 +/- 0.15) Ara-CTP retention up to now did not reach statistical significance (p = 0.12). CONCLUSIONS: The more rapid decrease of cellular Ara-CTP in T-cell leukemia and children at higher clinical risk groups provide a pharmacokinetic rationale for prolonged infusion duration as an alternative to the intensification by dose escalation alone.
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Authors | M Schiller, B Hohenlöchter, P Schulze-Westhoff, M Zimmermann, J Ritter, H Jürgens, J Boos |
Journal | Klinische Padiatrie
(Klin Padiatr)
1996 Jul-Aug
Vol. 208
Issue 4
Pg. 151-9
ISSN: 0300-8630 [Print] Germany |
Vernacular Title | Intrazelluläre Retention von Cytarabin-Triphosphat (Ara-CTP) in Blasten von Kindern mit akuter lymphoblastischer Leukämie. Korrelation zu klinischen Verlaufsparametern. |
PMID | 8926681
(Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cytarabine
- Arabinofuranosylcytosine Triphosphate
|
Topics |
- Adolescent
- Adult
- Arabinofuranosylcytosine Triphosphate
(pharmacokinetics)
- Blast Crisis
(blood, drug therapy, mortality)
- Bone Marrow
(drug effects, metabolism)
- Child
- Child, Preschool
- Cytarabine
(administration & dosage, pharmacokinetics)
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Female
- Humans
- Infant
- Leukemia, Myeloid, Acute
(blood, drug therapy, mortality)
- Male
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
(blood, drug therapy, mortality)
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
(blood, drug therapy, mortality)
- Prognosis
- Remission Induction
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