CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Larger numbers of CD4bright dendritic cells in donor bone marrow are associated with increased relapse after allogeneic bone marrow transplantation

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 CD341 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 HLAmatched 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). CD341 cells, T cells, B cells, natural killer cells, monocytes, and a rare population of CD32, CD4bright cells in the allografts were measured by flow cytometry. The CD32, CD4bright cells in bone marrow had the same frequency and phenotype as CD123bright 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, CD31 T cells, CD341 hematopoietic cells, and CD4bright cells as covariates for EFS, relapse, and nonrelapse mortality. Recipients of larger numbers of CD4bright cells had significantly lower EFS, a lower incidence of chronic graft-versushost disease (cGVHD), and an increased incidence of relapse. Recipients of larger numbers of CD341 cells had improved EFS; recipients of fewer CD341 cells had delayed hematopoietic engraftment and increased death from infections. In conclusion, the content of donor CD4bright 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. (Blood. 2001;97:2948-2956)