PREDICTION OF CHEMOTHERAPY RESPONSE IN HUMAN-LEUKEMIA USING AN INVITRO CHEMOTHERAPY SENSITIVITY TEST ON THE LEUKEMIC COLONY-FORMING CELLS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 55  (4) , 595-601
Abstract
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) was 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 [vincristine, cytosine arabinoside, prednisone, adriamycin, rubidazone and benzoylhydrazone daunorubicin] 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). 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 > 1.0 and 6 trials not resulting in complete remission had MSI < 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.