Hematopoietic growth factors after allogeneic marrow transplantation in animal studies and clinical trials.
The use of hematopoietic growth factors after allogeneic bone marrow transplantation (BMT) was investigated either in a preclinical canine model or in patients. G-CSF administration in dogs after high-dose total body irradiation (TBI) and transplantation of DLA-identical littermate marrow significantly accelerated recovery of peripheral blood neutrophils, monocytes and lymphocytes, but not of platelet counts, without significantly increasing the risks of graft failure or graft-versus-host disease (GVHD). GM-CSF given to patients after HLA-identical sibling BMT was well tolerated at doses < or = 250 micrograms/m2/day and resulted in significantly faster neutrophil recovery compared with matched historical controls. Risks of graft failure, GVHD or relapse were not increased. When GM-CSF was given after matched or 1-antigen mismatched unrelated BMTs, the number of febrile days and septic episodes within the first 28 days was reduced even though neutrophil recovery was not accelerated. Incidences of graft failure, GVHD or relapse were not increased. In recipients of BMT with invasive fungal infections, M-CSF in combination with conventional anti-fungal therapy may have a beneficial effect on survival. Treatment with GM-CSF in patients with graft failure appears to result in improved survival without increasing the risks of GVHD or relapse.
Schuening
F G
FG
Fred Hutchinson Cancer Research Center, Seattle, WA 98104-2092.
Nemunaitis
J
J
Appelbaum
F R
FR
Storb
R
R
D000328:Adult; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000401:mortality; D002986:Clinical Trials as Topic; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004285:Dogs; D004311:Double-Blind Method; D004353:Drug Evaluation, Preclinical; D006084:Graft Rejection / Q000188:drug therapy / Q000401:mortality; D006085:Graft Survival / Q000187:drug effects*; D006086:Graft vs Host Disease / Q000139:chemically induced; D006410:Hematopoiesis / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors / Q000009:adverse effects / Q000627:therapeutic use*; D006648:Histocompatibility; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D009181:Mycoses / Q000188:drug therapy / Q000209:etiology / Q000401:mortality; D011828:Radiation Chimera; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D016019:Survival Analysis; D014916:Whole-Body Irradiation
D000935:Antifungal Agents; D016298:Hematopoietic Cell Growth Factors; D006649:Histocompatibility Antigens; D011994:Recombinant Proteins