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.

Publication Type:

Journal Article

Source:

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K, Volume 19, Issue 5, p.822-8 (2005)

Keywords:

Adolescent, Adult, Aged, Antigens, CD34, Child, Child, Preschool, DISEASE PROGRESSION, Disease-Free Survival, Female, Graft Rejection, Graft Survival, Graft vs Host Disease, Hematologic Neoplasms, hematopoietic stem cell transplantation, Humans, Immunosuppressive Agents, Male, Middle Aged, Reproducibility of Results, Risk Factors, Survival Analysis, T-Lymphocytes, Transplantation Chimera, Transplantation Conditioning

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.