title: Recombinant human granulocyte-macrophage colony-stimulating factor accelerates neutrophil and monocyte recovery after allogeneic T-cell-depleted bone marrow transplantation.
abstract: In a prospective randomized study, five European transplant centers compared recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; mammalian glycosylated) with placebo. rhGM-CSF was administered in a dose of 8 micrograms glycoprotein (5.5 micrograms protein)/kg/d, as a continuous intravenous (IV) infusion for 14 days, starting 3 hours after bone marrow infusion. Fifty-seven patients entered and completed the study. Median age of the recipients was 34 years (range, 17 to 51 y). All donors were HLA-identical, MLC-nonreactive siblings. Marrow grafts were depleted of T lymphocytes either by counterflow centrifugation (n = 42) or by immunological methods (n = 15). Twenty-nine patients received rhGM-CSF and 28 patients placebo. The leukocyte count and the absolute neutrophil count were significantly higher in the rhGM-CSF-treated group from day +9 to day +14 after bone marrow transplantation (BMT). This was also true for the monocyte count from day +12 to day +21. Early neutrophil (greater than 0.1 and greater than 0.3 x 10(9)/L) and early leukocyte (greater than 0.3 and greater than 0.5 x 10(9)/L) recovery was significantly faster for the patients given GM-CSF. The incidences of graft-versus-host disease (GVHD) and transplant-related mortality were not different in both groups. However, the number of bronchopneumonias was significantly lower in the rhGM-CSF-treated group (P = .03). Long-term follow-up showed a trend to better overall disease-free survival at 2 years and a trend to a lower relapse risk in patients treated with rhGM-CSF. This study shows that rhGM-CSF significantly increases neutrophil and monocyte counts during periods of 6 to 10 days in the second and third week after BMT. This shortened period until myeloid cell recovery after transplantation resulted in a decreased number of pneumonias, without an increase in incidence of GVHD or relapse.
authors.affiliation: Department of Internal Medicine, University Hospital, Nijmegen, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: De Witte
authors.forename: A
authors.initials: A
authors.lastname: Gratwohl
authors.forename: N
authors.initials: N
authors.lastname: Van Der Lely
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: A C
authors.initials: AC
authors.lastname: Stern
authors.forename: B
authors.initials: B
authors.lastname: Speck
authors.forename: A
authors.initials: A
authors.lastname: Schattenberg
authors.forename: C
authors.initials: C
authors.lastname: Nissen
authors.forename: E
authors.initials: E
authors.lastname: Gluckman
authors.forename: W E
authors.initials: WE
authors.lastname: Fibbe
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000401:mortality; D006086:Graft vs Host Disease; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007239:Infections / Q000209:etiology; D007958:Leukocyte Count; D008212:Lymphocyte Depletion; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology*; D009504:Neutrophils / Q000166:cytology*; D011014:Pneumonia / Q000209:etiology / Q000517:prevention & control; D011994:Recombinant Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes
chemical_list: D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor