Larger numbers of CD4(bright) dendritic cells in donor bone marrow are associated with increased relapse after allogeneic bone marrow transplantation

Blood. 2001 May 15;97(10):2948-56. doi: 10.1182/blood.v97.10.2948.

Abstract

Relapse is the major cause of death after allogeneic bone marrow transplantation (BMT). This study tested the hypothesis that the numbers of donor mononuclear cells, lymphocytes, and CD34(+) cells influence relapse and event-free survival (EFS) after BMT. The study population consisted of 113 consecutive patients with hematologic malignancies who underwent non-T-cell-depleted BMT from HLA-matched siblings. Sixty-four patients had low-risk diagnoses (ALL/AML CR1, MDS RA/RARS, and CML CP1); 49 patients had high-risk diagnoses (all others). CD34(+) cells, T cells, B cells, natural killer cells, monocytes, and a rare population of CD3(-), CD4(bright) cells in the allografts were measured by flow cytometry. The CD3(-), CD4(bright) cells in bone marrow had the same frequency and phenotype as CD123(bright) type 2 dendritic cell (DC) progenitors, and they differentiated into typical DCs after short-term culture. Cox regression analyses evaluated risk strata, age, gender, and the numbers of nucleated cells, CD3(+) T cells, CD34(+) hematopoietic cells, and CD4(bright) cells as covariates for EFS, relapse, and nonrelapse mortality. Recipients of larger numbers of CD4(bright) cells had significantly lower EFS, a lower incidence of chronic graft-versus-host disease (cGVHD), and an increased incidence of relapse. Recipients of larger numbers of CD34(+) cells had improved EFS; recipients of fewer CD34(+) cells had delayed hematopoietic engraftment and increased death from infections. In conclusion, the content of donor CD4(bright) cells was associated with decreased cGVHD and graft-versus-leukemia effects in recipients of allogeneic bone marrow transplantation, consistent with a role for donor DCs in determining immune responses after allogeneic BMT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD34 / analysis
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / pathology*
  • Bone Marrow Transplantation*
  • CD3 Complex / analysis
  • CD4-Positive T-Lymphocytes / pathology*
  • Cell Count
  • Dendritic Cells / pathology*
  • Disease-Free Survival
  • Female
  • Graft vs Leukemia Effect
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy*
  • Humans
  • Male
  • Middle Aged
  • Recurrence
  • Stem Cells / pathology
  • Tissue Donors*
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Antigens, CD34
  • CD3 Complex