Cyclosporin A-induced cell kill in vitro in various clinical-hematologicaltypes of B-cell chronic lymphocytic leukemia

We investigated whether a known T cell modulator, Cyclosporin A (CyA) is al so toxic to chronic lymphocytic leukemia (B-CLL), in vitro. In contrast to seven other drugs and two types of irradiation the dose-response curves for CyA were very steep among the 36 CLL patients investigated, and the intrai ndividual variation of ID80 values was remarkably lower. The mode of CyA-in duced cell death was 'apoptotic-like' as indicated by flow cytometric analy sis, revealing cell condensation and annexin positivity. The partially smea ry DNA fragmentation pattern together with the relatively slow process of c ell death revealed a distinctive pattern of cell death in CLL. Leukemia cel ls from patients at an advanced clinical stage, of a diffuse histologic typ e and showing fast progression were the most sensitive to CyA. These new ob servations may have therapeutic implications in CLL. (C) 2000 Elsevier Scie nce Ltd. All rights reserved.