Prediction of chemotherapy response in human leukemia using an in vitro chemotherapy sensitivity test on the leukemic colony-forming cells.
An in vitro test system to quantitatively assess the chemotherapy sensitivity of human acute leukemic colony-forming cells (L-CFU) in relation to normal granulocytic precursor cells (CFU-C) has been developed. After simultaneous exposure of leukemic and normal bone marrow cells to individual drugs in vitro, cells were grown using an improved agar culture method with daily feeding. A sensitivity index (SI) was determined as the ratio of survival fraction of CFU-C to that of L-CFU, L-CFU being more (or less) sensitive than CFU-C if the SI were higher (or lower) than unity. Thirty SI were determined for 6 single drugs actually given in various combinations to a total of 9 patients (8 with acute nonlymphocytic leukemia and 1 with chronic myelomonocytic leukemia). A highly significant correlation was observed between high (or low) SI and achievement of (or failure to achieve) complete remission, with only 6 false correlations (p = 0.0013). Also, the mean of these SI (MSI) for the multiple single drugs given to each patient as components of a combination chemotherapy was used to indicate an overall sensitivity for each trial of the chemotherapy. Among the 10 chemotherapy trials (1 trial each for 8 patients and 2 trials for 1 patient), 4 trials resulting in complete remission had MSI higher than 1.0, and 6 trials not resulting in complete remission had MSI lower than 1.0 (p = 0.0048). This assay system appears useful in predicting the response of patients to chemotherapy and in the selection of the most effective drugs for use in individual patients.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002470:Cell Survival; D002478:Cells, Cultured; D003561:Cytarabine / Q000627:therapeutic use; D003630:Daunorubicin / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use
D000970:Antineoplastic Agents; D003561:Cytarabine; D014750:Vincristine; D004317:Doxorubicin; D011241:Prednisone; D003630:Daunorubicin