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

Leukemia. 2005 May;19(5):822-8. doi: 10.1038/sj.leu.2403718.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD34 / analysis
  • Antigens, CD34 / biosynthesis*
  • Child
  • Child, Preschool
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Graft Rejection / prevention & control*
  • Graft Survival
  • Graft vs Host Disease / prevention & control*
  • Graft vs Host Disease / therapy
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Reproducibility of Results
  • Risk Factors
  • Survival Analysis
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Transplantation Chimera / immunology
  • Transplantation Conditioning / methods*

Substances

  • Antigens, CD34
  • Immunosuppressive Agents