Recombinant granulocyte/macrophage-colony stimulating factor in human and murine bone marrow transplantation.
Recombinant granulocyte/macrophage-colony stimulating factor (rGM-CSF) is a protein that mediates a broad range of biological activities including inducing proliferation of bone marrow progenitor cells and up-regulating the functional capabilities of neutrophils, monocytes, and macrophages. We have administered rGM-CSF in vivo in the context of allogeneic (murine) and autologous (human) bone marrow transplantation (BMT). In a murine allogeneic model of T-cell depletion constructed to favor graft failure/rejection of donor marrow, ex vivo treatment of marrow with rGM-CSF significantly promoted engraftment. However, when rGM-CSF was infused in vivo, engraftment was significantly impaired. We have initiated a phase I clinical trial of rGM-CSF in human autologous BMT for patients with acute lymphoblastic leukemia (ALL). rGM-CSF has been administered for 14-21 days in a dose escalation study (16-128 micrograms/M2/day). At high doses of rGM-CSF, neutrophil recovery has returned earlier and to higher levels than previously observed in historical controls. rGM-CSF related toxicity in this study has been mild.
Blazar
B R
BR
Department of Pediatrics, University of Minnesota Hospital and Clinic, Minneapolis 55455.
Widmer
M B
MB
Kersey
J H
JH
Ramsay
N K
NK
McGlave
P B
PB
Urdal
D L
DL
Gillis
S
S
Henney
C
C
Vallera
D A
DA
D000293:Adolescent; D000328:Adult; D000818:Animals; D016026:Bone Marrow Transplantation; D002648:Child; D003115:Colony-Stimulating Factors / Q000627:therapeutic use* / Q000633:toxicity; D003131:Combined Modality Therapy; D004341:Drug Evaluation; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use* / Q000633:toxicity; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor