BIOLOGICAL AND CLINICAL-SIGNIFICANCE OF IN-VITRO PREDNISOLONE RESISTANCE IN ADULT ACUTE LYMPHOBLASTIC-LEUKEMIA

It has been reported that in vitro prednisolone (PDN) resistance provi des a prognostic value in childhood acute lymphoblastic leukaemia (ALL ). This study aimed at investigating the biological and clinical signi ficance of in vitro PDN resistance in adult ALL. Blast cells from 30 p atients were exposed to PDN (0.1 mu M-35 mu M) and cytotoxicity was de termined by the soluble tetrazolium formazan 2,3-bis 2-methoxy-4-nitro -5-sulphophenyl)-5-[(phenylamino) carbamyl]-2H-tetrazolium hydroxyde ( XTT) colorimetric assay. The IC50 (defined as the drug concentration t hat results in 50% growth inhibition) varied greatly among the samples , from 0.3 mu M to >35 mu M; 15 mu M was subsequently chosen as IC50-c ut-off point between in vitro resistant and sensitive cases. PDN-induc ed cytotoxicity was significantly related to apoptosis, as demonstrate d by regression analysis; in sensitive cases, however, the percentage of apoptotic cells after in vitro PDN treatment was significantly incr eased compared with control (p=0.002). Immunofluorescence evaluation o f intracellular BCL-2 protein showed an equal percentage of positive c ells in the two groups, but in resistant cells a higher mean fluoresce nce intensity (p=0.04) was demonstrated. In vitro sensitive and resist ant patients did not display differences in clinical characteristics, in cytological, karyotypic and immunophenotypic features and in the ou tcome of induction therapy. Disease-free survival (DFS), however, was significantly better in sensitive patients (p=0.02).