TOLERANCE EVALUATION OF L-ASPARAGINASE LOADED IN RED-BLOOD-CELLS

Objective: A pilot clinical study was conducted to evaluate the toxici ty of a single dose of L-asparaginase loaded in red blood cells (RBCs) . Methods: Thirteen patients received a single dose of L-asparaginase in the range 30-200 IU . kg(-1). The enzyme was loaded in one autologo us blood unit using a lysis-resealing process. A control population of 33 patients receiving L-asparaginase intravenously were tested in par allel. IgG, IgM and IgE class anti-L-asparaginase antibodies were dete cted using specific radioimmunoassays. Results: L-Asparaginase pharmac odynamic parameters may be greatly improved by administration of the d rug after internalisation in RBCs as compared to intravenous injection of free drug. The drug elimination was prolonged and similar to that of circulating carrier. After one injection of 30 IU . kg(-1) plasma L -asparagine was eliminated in 10 days and this was extended to 50 days for 150-200 IU . kg(-1) The drug was well tolerated and only transien t variations were observed for some of the biological parameters measu red. We did not reach the maximum tolerable dose (MTD) of L-asparagina se loaded in RBCs. No significant clinical toxicity was detected. In p articular, no immune adverse effects were observed. Conclusion: This s tudy opens new perspectives for the clinical utilisation of L-asparagi nase. This mode of administration of the drug is able to improve pharm acodynamic parameters and enzymic efficacy and to increase the general tolerance of the treatment.