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-factormobilized peripheral blood mononuclear cells (G-PBMC) (n ¼ 116) or marrow (n ¼ 14) transplantation after nonmyeloablative conditioning with 90 mg/m 2 fludarabine and 2 Gy TBI. The median number of CD34 þ cells transplanted was 6.5 Â 10 6 / kg. Higher numbers of grafted, and CD34 þ (P ¼ 0.0001) cells were associated with higher levels of day 28 donor T-cell chimerism. Higher numbers of CD14 þ (P ¼ 0.01) and CD34 þ (P ¼ 0.0003) cells were associated with rapid achievement of complete donor T-cell chimerism, while high numbers of CD8 þ (P ¼ 0.005) and CD34 þ (P ¼ 0.01) cells were associated with low probabilities of graft rejection. When analyses were restricted to G-PBMC recipients, higher numbers of grafted CD34 þ cells were associated with higher levels of day 28 donor T-cell chimerism (P ¼ 0.01), rapid achievement of complete donor T-cell chimerism (P ¼ 0.02), and a trend for lower risk for graft rejection (P ¼ 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 þ cells in unrelated grafts administered after nonmyeloablative conditioning.

A high proportion of donor CD4+ T cells expressing the lymph node-homing chemokine receptor CCR7 increases incidence and severity of acute graft-versus-host disease in patients undergoing allogeneic stem cell transplantation for hematological malignancy

“…53 It is conceivable that the higher number of CD34 þ cells in PBSC could generate more autoreactive post-thymic T cells, thereby increasing the risk of chronic GVHD and confounding the contribution of alloreactive CCR7 þ donor T cells. GVL activity and chronic (rather than acute) GVHD are often overlapping, [54][55][56] which might account in part for our observation that, like chronic GVHD, relapse was not significantly associated with the percentage of CD4 þ CCR7 þ T cells infused. Moreover, there are indications that GVHD can be separated from GVL effects.…”

The number of infused CD34+ cells does not influence the incidence of GVHD or the outcome of allogeneic PBSC transplantation, using reduced-intensity conditioning and antithymocyte globulin

“…Baron et al 22 analyzed the impact of graft composition on the outcome of 130 patients after allogeneic NST from unrelated donors. Conditioning consisted of fludarabine (90 mg/m 2 ) in combination with low-dose TBI (2 Gy), while for GVHD prophylaxis CYA plus mycophenolate-mophetil (MMF) was given.…”

Salvage haploidentical transplantation for graft failure using reduced-intensity conditioning

“…Immune rejection mediated by residual cellular immunity 1,2 or humoral immunity, 3,4 defects of the host BM microenvironment 5 and viral infections 6 are the main factors presumed to be involved in the occurrence of this complication. As immune rejection occurs as a result of the balance between residual host immunity and graft-derived immunity, the use of non-myeloablative or reduced-intensity conditioning (RIC), 7 T-cell depletion from the graft, 8 low numbers of infused progenitor cells 9,10 and immunological disparity (that is, HLA mismatch) 11 between the host and donor are known to increase the risk of graft failure. Although the overall frequency of graft failure is less than 5%, it has been reported to reach 12% for HLA-haploidentical SCT (haplo-SCT) 11 and is as high as 20% after cord blood transplantation (CBT).…”