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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

^a University of Maryland, Greenebaum Cancer Center, Baltimore, Maryland, USA;
^b Pharmacia Company, St. Louis, Missouri, USA

Key Words. Leridistim • Myelopoietin • Hematopoiesis • Radiation • Nonhuman primate

Correspondence: Ann M. Farese, M.S., University of Maryland, Greenebaum Cancer Center, Bressler Research Building, Room 7-047, 655 West Baltimore Street, Baltimore, Maryland 21201, USA. Telephone: 410-328-5347; Fax: 410-328-5488; e-mail: afarese{at}umaryland.edu

Leridistim is from the myelopoietin family of proteins, which are dual receptor agonists of the human interleukin-3 and G-CSF receptor complexes. This study investigated the effect of dosage, administration route, and schedule of leridistim to stimulate multilineage hematopoietic recovery in total body 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, every-other-day schedule at 200 µg/kg, or daily at 50 µg/kg, or i.v. daily or every-other-day schedules at 200 µg/kg dose. Other cohorts received G-CSF (Neupogen^® [Filgrastim]) in an every-other-day schedule at 100 µg/kg/day, or autologous serum (0.1%) s.c. daily. Hematopoietic recovery was assessed by bone marrow clonogenic activity, peripheral blood cell nadirs, duration of cytopenias, time to recovery to cellular thresholds, and requirements 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 trilineage hematopoietic recovery, and reduced antibiotic and transfusion requirements. 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 factor administered at the appropriate dose, route and schedule, stimulates multilineage hematopoietic reconstitution in radiation-myelosuppressed nonhuman primates.

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