title: Allogeneic peripheral blood stem cell graft composition affects early T-cell chimaerism and later clinical outcomes after non-myeloablative conditioning.
abstract: We have studied the influence of cell subsets [CD34, CD3, CD4, CD8, CD14, CD20, natural killer (NK; CD3(-)/CD56(+)), NKT (CD3(+)/CD56(+)), DC1, and DC2 cells] of granulocyte colony-stimulating factor mobilized peripheral blood stem cells (PBSC) on early T-cell chimaerism and later clinical outcomes in 125 patients with haematological malignancies who received human leucocyte antigen (HLA)-matched related grafts after non-myeloablative conditioning. Conditioning consisted of 2 Gy total body irradiation (TBI) alone (n = 28), or 2 Gy TBI preceded by either 90 mg/m(2) fludarabine (n = 62) or planned autologous haematopoietic cell transplantation (HCT) (n = 35). Post-transplant immunosuppression included mycophenolate mofetil and ciclosporin. Multivariate analysis showed that higher numbers of grafted NK cells predicted higher early T-cell chimaerism (P = 0.03), while higher numbers of B cells were associated with better clinical outcomes and a higher risk for chronic graft-versus-host disease (P = 0.05). Higher numbers of CD14(+) cells were associated with worse overall survival (P = 0.03), while higher numbers of CD34(+) cells showed better survival (P = 0.03). The addition of fludarabine or autologous HCT predicted higher early T-cell chimaerism (P = 0.001), while advanced donor age predicted lower chimaerism (P < or = 0.02). Patients with aggressive diseases were at higher risk for relapse/disease progression, and shorter progression-free and overall survival (P < 0.01). These results suggest that the dosing of certain cellular subsets of PBSC products can influence important outcomes post-HCT after non-myeloablative conditioning.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Panse
authors.forename: S
authors.initials: S
authors.lastname: Heimfeld
authors.forename: K A
authors.initials: KA
authors.lastname: Guthrie
authors.forename: M B
authors.initials: MB
authors.lastname: Maris
authors.forename: D G
authors.initials: DG
authors.lastname: Maloney
authors.forename: B B
authors.initials: BB
authors.lastname: Baril
authors.forename: M-T
authors.initials: MT
authors.lastname: Little
authors.forename: T R
authors.initials: TR
authors.lastname: Chauncey
authors.forename: B E
authors.initials: BE
authors.lastname: Storer
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.forename: B M
authors.initials: BM
authors.lastname: Sandmaier
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000276:immunology; D001402:B-Lymphocytes / Q000637:transplantation; D005500:Follow-Up Studies; D006086:Graft vs Host Disease; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007694:Killer Cells, Natural / Q000637:transplantation; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D015996:Survival Rate; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018183:Transplantation Chimera / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34; D018950:Lipopolysaccharide Receptors