This placebo-controlled study evaluated the efficacy of Flt-3 ligand (FL) combined with TPO in myelosuppressed rhesus monkeys. The monkeys were subjected to 5 Gy total body irradiation (TBI), resulting in 3 weeks of profound pancytopenia, and received either 5 μg/kg of rhesus TPO i.v. on d 1 (n = 4) and 100 μg/kg/d s.c. human FL (n = 4) or FL alone (n = 4) for 14 consecutive days and were compared with results from a concomitant study involving the administration of TPO alone (n = 4) or placebo (carrier; n = 4). The TPO/FL combination was considerably less effective than TPO alone, with a more profound nadir and a slower recovery to thrombocyte counts > 100 × 109/l, approaching recovery patterns of placebo controls. Leucocyte regeneration was similar in all animals. Monkeys treated with FL alone displayed a regeneration of reticulocytes and thrombocytes in the lower range of those of the placebo controls. Recovery of bone marrow (BM) cellularity was slightly accelerated in the TPO/FL-treated monkeys, but was not reflected by an increase in progenitor cells, in contrast to TPO alone. Monkeys treated with FL alone showed a BM reconstitution similar to placebo-treated controls. FL by itseff was not effective as a therapeutic agent in this model for myelosuppression. As FL also suppressed BM CD34+ cell reconstitution, we concluded that FL competed with TPO at the level of immature cell differentiation.

Flt3 ligand, Myelosuppression, Rhesus monkeys, Thrombocytes, TPO,
British Journal of Haematology
Department of Hematology

Hartong, S.C.C, Neelis, K.J, & Wagemaker, G. (2003). Co-administration of Flt-3 ligand counteracts the actions of thrombopoietin in myelosuppressed rhesus monkeys. British Journal of Haematology, 121(2), 359–367. doi:10.1046/j.1365-2141.2003.04283.x