title: High doses of transplanted CD34+ cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation.
abstract: This report examines the impact of graft composition on outcomes in 130 patients with hematological malignancies given unrelated donor granulocyte-colony-stimulating-factor-mobilized peripheral blood mononuclear cells (G-PBMC) (n = 116) or marrow (n = 14) transplantation after nonmyeloablative conditioning with 90 mg/m(2) fludarabine and 2 Gy TBI. The median number of CD34(+) cells transplanted was 6.5 x 10(6)/kg. Higher numbers of grafted CD14(+) (P = 0.0008), CD3(+) (P = 0.0007), CD4(+) (P = 0.001), CD8(+) (P = 0.004), CD3(-)CD56(+) (P = 0.003), and CD34(+) (P = 0.0001) cells were associated with higher levels of day 28 donor T-cell chimerism. Higher numbers of CD14(+) (P = 0.01) and CD34(+) (P = 0.0003) cells were associated with rapid achievement of complete donor T-cell chimerism, while high numbers of CD8(+) (P = 0.005) and CD34(+) (P = 0.01) cells were associated with low probabilities of graft rejection. When analyses were restricted to G-PBMC recipients, higher numbers of grafted CD34(+) cells were associated with higher levels of day 28 donor T-cell chimerism (P = 0.01), rapid achievement of complete donor T-cell chimerism (P = 0.02), and a trend for lower risk for graft rejection (P = 0.14). There were no associations between any cell subsets and acute or chronic GVHD nor relapse/progression. These data suggest more rapid engraftment of donor T cells and reduced rejection rates could be achieved by increasing the doses of CD34(+) cells in unrelated grafts administered after nonmyeloablative conditioning.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: F
authors.initials: F
authors.lastname: Baron
authors.forename: M B
authors.initials: MB
authors.lastname: Maris
authors.forename: B E
authors.initials: BE
authors.lastname: Storer
authors.forename: B M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: J P
authors.initials: JP
authors.lastname: Panse
authors.forename: T R
authors.initials: TR
authors.lastname: Chauncey
authors.forename: M
authors.initials: M
authors.lastname: Sorror
authors.forename: M-T
authors.initials: MT
authors.lastname: Little
authors.forename: D G
authors.initials: DG
authors.lastname: Maloney
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.forename: S
authors.initials: S
authors.lastname: Heimfeld
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control* / Q000628:therapy; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012307:Risk Factors; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018183:Transplantation Chimera / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D018952:Antigens, CD34; D007166:Immunosuppressive Agents