Evaluation of purine and pyrimidine analogues in human tumor cells from patients with low-grade lymphoproliferative disorders using the FMCA

The purine analogues fludarabine and cladribine (CdA) have recently become established to be effective treatment for low-grade non-Hodgkin's lymphoma (NHL). The pyrimidine nucleoside analogue cytarabine (AraC) has an importan t place in the treatment of acute leukemia, and gemcitabine is a new pyrimi din antimetabolite which has shown clinical activity against solid tumors. We have used the semiautomated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular h ydrolysis of fluorescein diacetate (FDA), to study these drugs. Eighty samp les from 60 patients with low-grade NHL were studied. Fifty samples from pa tients with acute lymphoid leukemia (ALL) and 118 samples from patients wit h acute myeloid leukemia (AML) were included for comparison. The results in dicate that the purine- and pyrimidine nucleoside analogues tested may be a s active against low-grade NHL as against acute leukemia. In low-grade NHL, AraC seems to be even more active in comparison to CdA (p=<0.0001) and flu darabine (p=0.001). Untreated patients were more drug sensitive than previo usly treated patients. Gemcitabine showed the highest correlation with AraC (0.90) whereas CdA showed the highest correlation with fludarabine (0.84). Based on these results we propose that AraC and gemcitabine may have a rol e in the treatment of low-grade NHL.