Abstract |
We evaluated in vitro the toxicity of idarubicin and its active metabolite idarubicinol on haematopoietic progenitors, using human umbilical cord blood and peripheral blood progenitors to obtain dose-response curves. We treated 16 patients with poor prognosis lymphoma in a phase I-II trial of high-dose idarubicin and melphalan and investigated if idarubicinol persisting in patients' plasma at the time of transplantation (day 0), on day +1 and +2 could result in an inhibition of infused progenitors. Colony inhibition was correlated with pharmacokinetic data and with the time of patients' engraftment. Plasma samples obtained before idarubicin treatment demonstrated a colony-stimulating effect, increasing the cloning efficiency by 72%. The inhibitory activity on colony forming unit granulocyte-macrophage (CFU-GM) of patients' plasma collected on the day of transplantation was lower than expected from dose-response curves (21% measured vs 70% expected). The time to patients' WBC and PLT recovery correlated with the amount of CD34+ cells reinfused and, to a lesser extent, with the colony-inhibiting effect of patients' plasma. The correlation between idarubicinol concentration and CFU-GM inhibition was not significant. These data suggest that plasma drug concentration on the day of stem cell reinfusion may overestimate the toxicity of residual anthracyclines to the transplanted cells.
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Authors | C Corsini, M Ghielmini, P Mancuso, F Tealdo, M Paolucci, M Zucchetti, P F Ferrucci, E Cocorocchio, M Mezzetti, A Mori, M Riggi, M D'Incalci, G Martinelli |
Journal | British journal of cancer
(Br J Cancer)
Vol. 82
Issue 3
Pg. 524-8
(Feb 2000)
ISSN: 0007-0920 [Print] England |
PMID | 10682659
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Antineoplastic Agents
- idarubicinol
- Daunorubicin
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Topics |
- Adult
- Antineoplastic Agents
(adverse effects)
- Daunorubicin
(adverse effects, analogs & derivatives, blood, pharmacokinetics)
- Hematopoietic Stem Cells
(drug effects)
- Hodgkin Disease
(drug therapy)
- Humans
- Lymphoma, Non-Hodgkin
(drug therapy)
- Middle Aged
- Treatment Outcome
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