MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR ACCELERATES PLATELET RECOVERY IN PERIPHERAL-BLOOD PROGENITOR-CELL TRANSPLANT RECIPIENTS

We have investigated the potential of PEGylated recombinant human mega karyocyte growth and development factor (PEG-rHuMGDF), a molecule rela ted to thrombopoietin (mpl ligand or TPO) in minimizing the thrombocyt openia associated with hematopoietic ablation and peripheral blood pro genitor cell (PBPC) transplant, Irradiated mice that received PBPC mob ilized by PEG-rHuMGDF or granulocyte colony-stimulating factor (G-CSF) had a reduced number of thrombocytopenic days with platelets below 10 0 x 10(6) per mt of blood, Recipients of unmobilized PBPC had a 9 day thrombocytopenic phase which was shortened to 7 days if they were give n granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPC. This was further reduced to 2 or 3 days of thrombocytopenia in r ecipients of G-CSF- or PEG-MGDF-mobilized PBPC. Despite our observatio n that PEG-rHuMGDF is a relatively modest stimulator of the mobilizati on of myeloid progenitors to the blood, MGDF-mobilized PBPC do effect accelerated recovery of platelets after transplantation. However, the most effective use of PEG-rHuMGDF is when it is given during the recov ery phase after PBPC transplantation to hematopoietically ablated mice . Posttransplant treatment with PEG-rHUMGDF reduces thrombocytopenia t o a single day or less, in recipients of most types of PBPC, Mice that were treated during the first 2 weeks after PBPC transplant with PEG- rHuMGDF had 1 thrombocytopenic day compared to 9 days in carrier-treat ed recipients of unmobilized PBPC and 2 to 3 days in carrier-treated r ecipients of the optimally mobilized PBPC from G-CSF or G-CSF/PEG-rHuM GDF treated donors. In groups where PEG-rHuMGDF was included in the mo bilization protocol and used to treat recipients as well thrombocytope nia was effectively eliminated, These data show that PEG-rHuMGDF is a highly effective agent in eliminating the thrombocytopenia associated with PBPC transplantation. (C) 1996 by The American Society of Hematol ogy.