New TPO treatment schedules of increased safety and efficacy: pre-clinical validation of a thrombopoiesis simulation model.

Thrombopoietin (TPO) immunogenicity hampers its development as a therapeutic agent for attenuating thrombocytopenia and improving platelet harvest in donors. This work was aimed at validating, in mouse and in monkey experiments, a thrombopoiesis computer-model prediction that platelet counts, similar to those obtained with accepted TPO dose scheduling, can also be achieved by new and safer schedules of significantly reduced doses. To this end we compared, in a two-arm mouse experiment, platelet increases obtained with a single intraperitoneal dosing of recombinant mouse TPO (17.