Relationship between the in vitro sensitivity to cytosine arabinoside of blast progenitors and the outcome of treatment in acute myeloblastic leukaemia patients.

The sensitivity to cytosine arabinoside (Ara-C) of blast progenitors from 22 acute myeloblastic leukaemia (AML) patients was studied in methylcellulose and suspension cultures. Primary colony-formation (PE1) in methylcellulose reflects the terminal divisions of blast progenitors, while secondary colony formation (PE2) in methylcellulose and the clonogenic cells recovery in suspension are considered to be based on the self-renewal of blast progenitors. In any patient, PE2 or clonogenic cells in suspension were more sensitive to Ara-C than PE1. The results indicate that Ara-C effectively suppresses not only terminal divisions but also self-renewal of blast progenitors D10 Ara-C value, the dose required to reduce survival to 10% of control, for PE1, PE2 and clonogenic cells in suspension showed marked patient-to-patient variation. No significant correlation was found between D10 Ara-C in methylcellulose or suspension culture and the response to treatment with a combination chemotherapy of 6-mercaptopurine, Ara-C and daunorubicin. However, a relapsed patient whose D10 values in methylcellulose and suspension cultures were very high showed poor response to a high-dose Ara-C protocol, where Ara-C was given alone at a high dose. The application of chemosensitivity test as a prediction of the clinical outcome may be dependent on the treatment protocol.