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.