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

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 2Gy 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

Chimerism and outcomes after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning

Allogeneic hematopoietic cell transplantation ( HCT) following nonmyeloablative conditioning has been extensively evaluated in patients with hematologic malignancies who are ineligible for conventional HCT because of age or medical comorbidities. Nonmyeloablative regimens have led to an initial state of mixed hematopoietic chimerism defined as coexistence of donor- and host-derived hematopoiesis. While nonmyeloablative regimens have been associated with reduced regimen-related toxicities in comparison with conventional myeloablative conditioning, graft rejection, graft-versus-host disease ( GVHD), and disease progression have remained significant challenges. In this article, after briefly introducing current techniques for chimerism assessment, we describe factors affecting donor chimerism levels after nonmyeloablative conditioning, and then review data suggesting that chimerism assessment early after HCT might help identify patients at risk for graft rejection, GVHD and relapse/progression. Finally, we discuss how these observations have opened the way to further research protocols evaluating manipulation of postgrafting immunosuppression, and/or infusion of donor immune cells