In vitro sensitivity of myeloblast clonogenic cells to doxorubicin, aclacinomycin A, and 4'-O-tetrapyranyl-doxorubicin: correlations with clinical responses.
The in vitro sensitivity of peripheral blood myeloblast clonogenic cells (CFU-MLs) to doxorubicin (DOX), aclacinomycin (ACL), and 4'-O-tetrapyranyl-doxorubicin (THP-DOX) was studied to evaluate the individual chemosensitivity of CFU-MLs. CFU-MLs from untreated patients were sensitive to the three tested anthracyclines (in 60% to 69% of the patients). Conversely, CFU-MLs from relapsed patients previously treated with DOX-containing regimens were sensitive to ACL and THP-DOX (in 71% and 75% of the patients, respectively) but resistant to DOX. Six of ten patients who entered complete remission with a combination of DOX, vincristine, and cytosine arabinoside had CFU-MLs in vitro which were sensitive to DOX. Conversely, none of the 13 patients resistant to this chemotherapy regimen displayed CFU-MLs which were sensitive in vitro to DOX. Nine of ten patients who responded to ACL as well as one of three resistant patients had CFU-MLs sensitive to ACL in vitro. No clinical responses were observed with THP-DOX in five of seven patients with CFU-MLs sensitive to this drug. The results indicate that myeloblast clonogenic assays can be used to predict the in vitro sensitivity of CFU-MLs to compounds with established antileukemic activity (ie, DOX, ACL). However, the discrepancy between in vitro and in vivo sensitivity to THP-DOX underlines the importance of knowledge of drug pharmacokinetics and the difficulty of using the CFU-ML test for screening new drugs.
D015250:Aclarubicin; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D007938:Leukemia / Q000188:drug therapy*; D009279:Naphthacenes / Q000494:pharmacology / Q000627:therapeutic use; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects*; D014410:Tumor Stem Cell Assay
D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; D015250:Aclarubicin; D004317:Doxorubicin; C027260:pirarubicin