Prediction of chemotherapy response in human leukemia using an in vitro
chemotherapy sensitivity test on the leukemic colony-forming cells
CH Park, M Amare, MA Savin, JW Goodwin, MM Newcomb and B Hoogstraten
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.
Volume 55,
Issue 4,
pp. 595-601,
04/01/1980
Copyright © 1980 by The American Society of Hematology
