title: Larger numbers of CD4(bright) dendritic cells in donor bone marrow are associated with increased relapse after allogeneic bone marrow transplantation.
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.
authors.affiliation: Bone Marrow and Stem Cell Transplant Center, Division of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: E K
authors.initials: EK
authors.lastname: Waller
authors.forename: H
authors.initials: H
authors.lastname: Rosenthal
authors.forename: T W
authors.initials: TW
authors.lastname: Jones
authors.forename: J
authors.initials: J
authors.lastname: Peel
authors.forename: S
authors.initials: S
authors.lastname: Lonial
authors.forename: A
authors.initials: A
authors.lastname: Langston
authors.forename: I
authors.initials: I
authors.lastname: Redei
authors.forename: I
authors.initials: I
authors.lastname: Jurickova
authors.forename: M W
authors.initials: MW
authors.lastname: Boyer
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology*; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D002452:Cell Count; D003713:Dendritic Cells / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D020544:Graft vs Leukemia Effect; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D013234:Stem Cells / Q000473:pathology; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex