AN ANALYSIS OF THE EFFECTS OF COMBINED TREATMENT WITH RMGM-CSF AND PEG-RHUMGDF IN MURINE BONE-MARROW TRANSPLANT RECIPIENTS

We have studied the potential of combination growth factor treatment w ith GM-CSF and megakaryocyte growth and development factor (MGDF) to s timulate hematopoietic recovery in mice following bone marrow transpla ntation. More rapid recovery of neutrophils occurred in mice treated w ith recombinant murine (rm)GM-CSF plus pegylated recombinant human (PE G-rHu)MGDF than carrier treated controls, however this recovery was eq uivalent to the effect of treatment with rmGM-CSF alone, PEG-rHuMGDF s timulated a more rapid recovery of platelets with no effect on neutrop hil recovery, At the two tested doses of rmGM-CSF (72 and 200 mu g/kg/ day) the platelet recovery was inferior to that in carrier treated mic e, Also, the addition of rmGM-CSF to PEG-rHuMGDF had a dose-related ne gative impact on platelet recovery compared to PEG-rHuMGDF alone, Thes e data suggest that the use of combination therapy in some clinical in dications may lead to unexpected results, Furthermore, careful dosage studies may be necessary to identify the full potential of combined gr owth factors to obtain additive or synergistic effects on multilineage hematopoietic reconstitution in vivo.