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

• Published in: Blood 2001-05, Vol.97 (10), p.2948-2956
• Main Authors: Waller, E K, Rosenthal, H, Jones, T W, Peel, J, Lonial, S, Langston, A, Redei, I, Jurickova, I, Boyer, M W
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0006-4971
• DOI: 10.1182/blood.V97.10.2948

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.