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.

, , , ,,
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