Allogeneic peripheral blood stem cell graft composition affects early T-cell chimaerism and later clinical outcomes after non-myeloablative conditioning.
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.
Panse
J P
JP
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Heimfeld
S
S
Guthrie
K A
KA
Maris
M B
MB
Maloney
D G
DG
Baril
B B
BB
Little
M-T
MT
Chauncey
T R
TR
Storer
B E
BE
Storb
R
R
Sandmaier
B M
BM
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
D018952:Antigens, CD34; D018950:Lipopolysaccharide Receptors