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 with GM-CSF and megakaryocyte growth and development factor (MGDF) to stimulate hematopoietic recovery in mice following bone marrow transplantation. More rapid recovery of neutrophils occurred in mice treated with recombinant murine (rm)GM-CSF plus pegylated recombinant human (PEG-rHu)MGDF than carrier treated controls, however this recovery was equivalent to the effect of treatment with rmGM-CSF alone. PEG-rHuMGDF stimulated a more rapid recovery of platelets with no effect on neutrophil recovery. At the two tested doses of rmGM-CSF (72 and 200 microg/kg/day) the platelet recovery was inferior to that in carrier treated mice. Also, the addition of rmGM-CSF to PEG-rHuMGDF had a dose-related negative impact on platelet recovery compared to PEG-rHuMGDF alone. These data suggest that the use of combination therapy in some clinical indications may lead to unexpected results. Furthermore, careful dosage studies may be necessary to identify the full potential of combined growth factors to obtain additive or synergistic effects on multilineage hematopoietic reconstitution in vivo.
Molineux
G
G
Amgen, Inc., Department of Developmental Hematology, Thousand Oaks, California 91320, USA.
Hartley
C
C
McElroy
P
P
McCrea
C
C
Kerzic
P
P
McNiece
I
I
D000818:Animals; D016026:Bone Marrow Transplantation; D002452:Cell Count / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004906:Erythrocyte Count / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007279:Injections, Subcutaneous; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009000:Monocytes / Q000166:cytology; D010976:Platelet Count / Q000187:drug effects; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013926:Thrombopoietin / Q000008:administration & dosage / Q000494:pharmacology*
D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013926:Thrombopoietin