Idarubicinol myelotoxicity: a comparison of in vitro data with clinical outcome in patients treated with high-dose idarubicin.
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.
Corsini
C
C
Hemato/Oncology Department, European Institute of Oncology, Milan, Italy.
Ghielmini
M
M
Mancuso
P
P
Tealdo
F
F
Paolucci
M
M
Zucchetti
M
M
Ferrucci
P F
PF
Cocorocchio
E
E
Mezzetti
M
M
Mori
A
A
Riggi
M
M
D'Incalci
M
M
Martinelli
G
G
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D003630:Daunorubicin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008875:Middle Aged; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C054440:idarubicinol; D003630:Daunorubicin