DC2 effect on survival following allogeneic bone marrow transplantation.
The graft-vs-tumor effect is an important part of the curative potential of allogeneic transplantation. We characterized the effect of transplanted donor mononuclear cells on relapse- and event-free survival after allogeneic bone marrow transplantation (BMT). We studied 113 consecutive patients with hematologic malignancies who received non-T-cell-depleted BMT from human leukocyte antigen (HLA)-matched siblings. Most patients (n = 103) received busulfan (Myleran)-based conditioning, and all patients received standard short-course methotrexate and tacrolimus (Prograf) as graft-vs-host disease prophylaxis. Sixty-four patients had low-risk diagnoses (acute lymphoblastic leukemia/acute myeloid leukemia [first complete remission], myelodysplastic syndrome [refractory anemia/refractory anemia with ring sideroblasts], and chronic myeloid leukemia [first chronic phase]); 49 patients had high-risk diagnoses (all others). Cox regression analyses evaluated risk strata, age, gender, and the numbers of nucleated cells, CD3-positive T cells, CD34-positive hematopoietic cells, and type 2 dendritic cells (DC2) as covariates for event-free survival, relapse, and nonrelapse mortality. Recipients of larger numbers of DC2 cells had significantly lower event-free survival, a lower incidence of chronic graft-vs-host disease, and an increased incidence of relapse. Recipients of larger numbers of CD34-positive cells had improved event-free survival; recipients of fewer CD34-positive cells had delayed hematopoietic engraftment and increased death from infections. In conclusion, content of donor DC2 cells was associated with decreased chronic graft-vs-host disease and graft-vs-leukemia effects consistent with Th2/Tc2 polarization of donor Tcells following allogeneic bone marrow transplantation.
Waller
Edmund K
EK
Bone Marrow and Stem Cell Transplant Center, Emory University, Atlanta, Georgia 30322, USA.
Rosenthal
Hilary
H
Sagar
Lonial
L
D018952:Antigens, CD34 / Q000378:metabolism; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology*; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D007938:Leukemia / Q000276:immunology / Q000628:therapy*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D018952:Antigens, CD34; D017252:CD3 Complex