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 bloo d and peripheral blood progenitors to obtain dose-response curves. We treat ed 16 patients with poor prognosis lymphoma in a phase I-Il trial of high-d ose 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' engraf tment. Plasma samples obtained before idarubicin treatment demonstrated a c olony-stimulating effect, increasing the cloning efficiency by 72%. The inh ibitory activity on colony forming unit granulocyte-macrophage (CFU-GM) of patients' plasma collected on the day of transplantation was tower than exp ected from dose-response curves (21% measured vs 70% expected). The time to patients' WBC and PLT recovery correlated with the amount of CD34+ cells r einfused and, to a lesser extent, with the colony-inhibiting effect of pati ents' plasma. The correlation between idarubicinol concentration and CFU-GM inhibition was not significant. These data suggest that plasma drug concen tration on the day of stem cell reinfusion may overestimate the toxicity of residual anthracyclines to the transplanted cells. (C) 2000 Cancer Researc h Campaign.