Effects of Recombinant Human Thrombopoietin (rhTPO) on Thrombopoiesis in Bone Marrow-Transplanted Mice

Summary

We examined whether recombinant human thrombopoietin (rhTPO) is capable of preventing thrombocytopenia and promoting thrombopoietic reconstitution following bone marrow transplantation (BMT) in mice. Immediately after receiving 10Gy whole-body irradiation, 7-weekold male C3H/HeN mice were inoculated with 10⁶ bone marrow cells obtained from syngeneic mice (day 0). In control mice undergoing BMT, platelet counts decreased below 5% of the normal counts with a nadir on day 10, and then returned to the normal level on day 28. Consecutive treatment with rhTPO at daily doses of 3 to 300μ/kg s.c. from day 1 significantly prevented thrombocytopenia on day 10, and promoted the recovery on day 14 in a dose-dependent manner. A plateau was achieved by consecutive subcutaneous injections of 30μg/kg. Variations in white blood cell counts and hemoglobin concentration following BMT were not influenced by the rhTPO-treatment. We, then, investigated the administration schedule of rhTPO in this model. rhTPO-injection starting from day 5 did not prevent thrombocytopenia on days 10 and 12 after BMT, but enhanced the recovery on day 14. Furthermore, administration with rhTPO on alternate days at 55.7.μg/kg/day for 7 days or at an interval of two days at 78μg/kg/day for 4 days was less effective than consecutive administration at 30μg/kg/day for 13 days. These findings suggest the usefulness of consecutive treatment with rhTPO from day 1 after BMT.