A single dose of pegylated leridistim significantly improves neutrophil recovery in sublethally irradiated rhesus macaques

Leridistim, a member of the myelopoietin family of dual receptor agonists t hat binds interleukin-3 and G-CSF receptors, has been shown to enhance hema topoietic activity in rhesus monkeys above that observed with either cytoki ne alone or in combination. This study demonstrated the ability of a pegyla ted form of leridistim (peg-leridistim), administered s.c., as a single- or two-dose regimen separated by 4 or 7 days, to significantly improve neutro phil recovery following radiation-induced myelosuppression. Rhesus macaques were total body x irradiated (250 kVp, TBI) to 600 cGy. Following TBI, two groups received peg-leridistim (n = 5) or leridistim (n = 4) at a dose of 600 mug/kg on day 1, while two other groups (both n = 4) received peg-lerid istim at 200 mug/kg on day 1 and day 4, or day 1 and day 7. The irradiation controls (n = 7) received 0.1 % autologous serum for 18 days. All peg-leri distim treatment schedules significantly improved all neutrophil-related pa rameters following TBI as compared with nontreated controls and were equiva lent in effect when compared among themselves. Administration of a single h igh dose or two separate lower doses of peg-leridistim significantly improv ed neutrophil regeneration, in a manner equal to that of conventional daily or abbreviated every-other-day administration of leridistim in this nonhum an primate model of severe myelosuppression.