Improvement of thrombocytopenia following bone marrow transplantation by pegylated recombinant human megakaryocyte growth and development factor in mice.

Abstract

We examined whether pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) is capable of improving thrombocytopenia and promoting thrombopoietic reconstitution following lethal irradiation and bone marrow transplantation (BMT) in mice. Immediately after receiving 10 Gy whole body irradiation (day 0), male C3H/HeN mice were inoculated with 10(6) bone marrow cells obtained from syngeneic mice. Circulating platelet counts decreased to below 4% of the normal counts with a nadir on day 10, and then returned to the normal level on day 28 in the control mice undergoing BMT. Subcutaneous consecutive treatment with PEG-rHuMGDF at doses from 10 to 300 micrograms/kg/day from day 1 for 13 days significantly improved the platelet nadir and promoted platelet recovery. The white blood cell counts and hemoglobin concentration following BMT were not influenced by the PEG-rHuMGDF. PEG-rHuMGDF-injection starting from day 5 did not improve the platelet nadir following BMT. Furthermore, administration with PEG-rHuMGDF on alternate days at 55.7 micrograms/kg/day for 7 days or at an interval of 3 days at 78 micrograms/kg/day for 4 days (twice a week for 2 weeks) had a significant efficacy, but these administration regimens had less efficacy than consecutive administration at 30 micrograms/kg/day for 13 days. The numbers of megakaryocytes and megakaryocyte progenitor cells decreased to 5 and 0.2% of normal level, respectively, in the control mice. Consecutive administration of PEG-rHuMGDF enhanced the recovery of the mean number of these cells compared to those in vehicle-treated mice, although such effects were not statistically significant except for the number of megakaryocyte progenitors on day 12. These results suggest that consecutive treatment with PEG-rHuMGDF beginning from the day after BMT may be effective in improving thrombocytopenia following BMT.

• Authors: K Kabaya, K Shibuya, Y Torii, Y Nitta, M Ida, H Akahori, T Kato, M Kusaka, H Miyazaki
• Journal: Bone marrow transplantation (Bone Marrow Transplant) Vol. 18 Issue 6 Pg. 1035-41 (Dec 1996) ISSN: 0268-3369 [Print] England
• PMID: 8971370 (Publication Type: Journal Article)

Chemical References

• Recombinant Proteins
• polyethylene glycol-recombinant human megakaryocyte growth and development factor
• Polyethylene Glycols
• Thrombopoietin

Topics

• Animals
• Bone Marrow Transplantation
• Drug Administration Schedule
• Drug Evaluation, Preclinical
• Male
• Mice
• Mice, Inbred C3H
• Platelet Count (drug effects)
• Polyethylene Glycols (administration & dosage, therapeutic use)
• Radiation Chimera
• Recombinant Proteins (administration & dosage, therapeutic use)
• Thrombocytopenia (drug therapy, etiology)
• Thrombopoietin (administration & dosage, therapeutic use)
• Transplantation Conditioning (adverse effects)
• Whole-Body Irradiation (adverse effects)