title: CD34 cell dose in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell grafts affects engraftment kinetics and development of extensive chronic graft-versus-host disease after human leukocyte antigen-identical sibling transplantation.
abstract: A retrospective analysis of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cell (G-PBMC) products harvested from healthy donors indicates significant variability in both the absolute number and relative proportion of CD34, CD3, and CD14 cells obtained. This report examined whether variations in the cellular composition of G-PBMC products correlated with clinical outcomes after myeloablative allogeneic transplantation. The numbers of CD34, CD3, and CD14 cells infused into 181 human leukocyte antigen (HLA)-identical sibling recipients were analyzed with respect to tempo of engraftment, acute graft-versus-host-disease (GVHD), clinical extensive chronic GVHD, overall survival, and disease relapse. Neither acute GVHD, overall survival, nor disease relapse was statistically significantly associated with CD34, CD3, or CD14 cell doses or the CD14 to CD3 ratio. CD3 and CD14 cell doses and CD14 to CD3 ratios did not correlate with the tempo of neutrophil and platelet engraftment. However, increasing CD34 cell numbers were significantly associated with accelerated neutrophil (P =.03) and platelet (P =.01) engraftment. Higher doses of CD34 cells (> 8.0 x 10(6)/kg) were also associated with a significantly increased hazard of clinical extensive chronic GVHD (HR = 2.3, 95% confidence interval [CI] 1.4-3.7, P =.001), but neither CD3 nor CD14 doses were statistically significantly associated with chronic GVHD. It was concluded that CD34 cell dose in G-PBMC grafts appears to affect both the engraftment kinetics and the development of clinical extensive chronic GVHD in HLA-identical sibling recipients but without a demonstrable impact on survival, relapse, and acute GVHD. Given the morbidity associated with extensive chronic GVHD, efforts to further accelerate engraftment in HLA-matched sibling transplants by increasing CD34 cell number in G-PBMC products may be counterproductive.
authors.affiliation: Fred Hutchinson Cancer Research Center, the University of Washington, and the Veterans Affairs Medical Center, Seattle, WA 98109-1024, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Zaucha
authors.forename: T
authors.initials: T
authors.lastname: Gooley
authors.forename: W I
authors.initials: WI
authors.lastname: Bensinger
authors.forename: S
authors.initials: S
authors.lastname: Heimfeld
authors.forename: T R
authors.initials: TR
authors.lastname: Chauncey
authors.forename: R
authors.initials: R
authors.lastname: Zaucha
authors.forename: P J
authors.initials: PJ
authors.lastname: Martin
authors.forename: M E
authors.initials: ME
authors.lastname: Flowers
authors.forename: J
authors.initials: J
authors.lastname: Storek
authors.forename: G
authors.initials: G
authors.lastname: Georges
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.forename: B
authors.initials: B
authors.lastname: Torok-Storb
mesh_terms: D000208:Acute Disease; D018952:Antigens, CD34 / Q000032:analysis*; D017252:CD3 Complex / Q000032:analysis; D002452:Cell Count; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006680:HLA Antigens / Q000032:analysis; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D007700:Kinetics; D007958:Leukocyte Count; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D009504:Neutrophils; D009679:Nuclear Family; D010976:Platelet Count; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex; D006680:HLA Antigens; D018950:Lipopolysaccharide Receptors; D016179:Granulocyte Colony-Stimulating Factor