Interaction of cyclosporin A and etoposide. Clinical and in vitro assessment in blast phase of chronic myeloid leukaemia.

Abstract

Combination chemotherapy has had a low impact on survival of blast crises in chronic myelogeneous leukaemia (CML) which may be due to drug resistance. This work attempted to correlate the clinical response and some experimental evidence for the MDR phenotype. Blast cells were positive for P-glycoprotein using APAAP assay. In vitro tests showed that etoposide was partially toxic to blast cells when used alone but had its toxicity increased by nearly sixfold when combined with cyclosporin A (CSA). The patient responded poorly to treatment with etoposide combined with mitoxantrone and high-dose ara-c. However, when etoposide was associated with CSA, this patient returned to the chronic phase reinforcing our in vitro studies. Because no serious toxicity was seen clinically, we are inclined to consider the circumvention protocol an useful strategy to treat blast crises of CML.