Leridistim, a chimeric dual G-CSF and IL-3 receptor agonist, enhances multilineage hematopoietic recovery in a nonhuman primate model of radiation-induced myelosuppression: Effect of schedule, dose, and route of administration

Leridistim is from the myelopoietin family of proteins, which are dual rece ptor agonists of the human interleukin-3 and G-CSF receptor complexes. This study investigated the effect of dosage, administration route, and schedul e of leridistim to stimulate multilineage hematopoietic recovery in total b ody irradiated rhesus monkeys. Animals were x-irradiated on day 0 (600 cGy, 250 kVp) and then received, on day 1, leridistim s.c. in an abbreviated, e very-other-day schedule at 200 mug/kg, or daily at 50 mug/kg, or i.v. daily or every-other-day schedules at 200 mug/kg dose. Other cohorts received G- CSF (Neupogen (R) [Filgrastim]) in an every-other-day schedule at 100 mug/k g/day, or autologous serum (0.1 %) s.c. daily. Hematopoietic recovery was a ssessed by bone marrow clonogenic activity, peripheral blood cell nadirs, d uration of cytopenias, time to recovery to cellular thresholds, and require ments for clinical support. Leridistim, administered s.c. every other day, or i.v. daily, significantly improved neutrophil, platelet, and lymphocyte nadirs, shortened the respective durations of cytopenia, hastened trilineag e hematopoietic recovery, and reduced antibiotic and transfusion requiremen ts. A lower dose of leridistim administered daily s.c. enhanced recovery of neutrophil and platelet parameters but did not affect lymphocyte recovery relative to controls. Leridistim, a novel engineered hematopoietic growth f actor administered at the appropriate dose, route and schedule, stimulates multilineage hematopoietic reconstitution in radiation-myelosuppressed nonh uman primates.