In vitro sensitivity of myeloblast clonogenic cells to doxorubicin, aclacinomycin A, and 4'-O-tetrapyranyl-doxorubicin: correlations with clinical responses.

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Abstract
The in vitro sensitivity of peripheral blood myeloblast clonogenic cells (CFU-ML) to doxorubicin (DOX), aclacinomycin (ACL), and 4''-O-tetrapyranyl-doxorubicin (THP-DOX) was studied to evaluate the individual chemosensitivity of CFU-ML. CFU-ML from untreated patients were sensitive to the 3 tested anthracyclines (in 60-69% of the patients). Conversely, CFU-ML from relapsed patients previously treated with DOX-containing regimens were sensitive to ACL and THP-DOX (in 71 and 75% of the patients, respecively) but resistant to DOX. Six of 10 patients who entered complete remission with a combination of DOX, vincristine, and cytosine arabinoside had CFU-ML in vitro which were sensitive to DOX. Conversely, none of the 13 patients resistant to this chemotherapy regimen displayed CFU-ML which were sensitive in vitro to DOX. Nine of 10 patients who responded to ACL as well s 1 of 3 resistant patients had CFU-ML sensitive to ACL in vitro. No clinical responses were observed with THP-DOX in 5 of 7 patients with CFU-ML sensitive to this drug. Myeloblast clonogenic assays can be used to predict the in vitro sensitivity of CFU-ML to compounds with established antileukemic activity (i.e., DOX, ACL). 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.