Higher Marrow Levels of Plasmacytoid Dendritic Cells and Naive T Cells in Unrelated Donors Associated With Increased Survival in Stem Cell Transplant
In a study reported in the Journal of Clinical Oncology, Waller et al found that higher marrow graft, but not peripheral blood graft, levels of plasmacytoid dendritic cells and naive CD4-positive and CD8-positive T cells in unrelated donors were associated with increased overall survival in patients with hematologic malignancy receiving hematopoietic stem cell transplants.
Study Details
The study involved analysis of fresh aliquots of 161 bone marrow and 147 peripheral blood stem cell allografts from among 551 North American pairs of unrelated donors and corresponding leukemia, myelodysplasia, or myelofibrosis patients aged < 66 years with planned allogeneic transplantation in the BMTCTN 0201 trial. Levels of immune cell subsets in donor bone marrow stem cells and peripheral blood stem cells mobilized by granulocyte colony-stimulating factor were analyzed for relationship to clinical outcome in transplant recipients.
The bone marrow and peripheral blood stem cell groups were generally balanced for recipient age (eg, 19%, 14%, 18%, and 22% vs 20%, 19%, 22%, and 22% for ages 21–30, 31–40, 41–50, and 51–60 years), recipient sex (64% and 58% male), recipient cytomegalovirus (CMV) status (55% and 46% positive), Karnofsky performance status (90–100 in 67% and 60%), primary disease (acute myelogenous leukemia in 42% and 53%, acute lymphoblastic leukemia in 25% and 20%, chronic myelogenous leukemia in 10% and 14%, myelodysplastic syndrome in 22% and 10%), disease risk (high in 24% and 29%), conditioning regimen (cyclophosphamide/total-body irradiation in 47% and 48%, busulfan [Busulfex, Myleran]/cyclophosphamide in 30% and 29%, fludarabine/busulfan/antithymocyte globulin in 18% and 17%), graft vs host disease prophylaxis (cyclosporine/methotrexate in 24% and 18%, tacrolimus/methotrexate in 67% and 76%).
The groups were also generally balanced for donor age (eg, 42%, 33%, and 21% vs 39%, 29%, and 24% for ages 18–30, 31–40, and 41–50 years), donor sex (68% and 63% male), donor CMV status (33% and 38% positive), and number of HLA mismatches at HLA-A, B, C, and DRB1 (0 in 75% and 80%, 1 in 20% and 18%, 2 in 4% and 1%, 3 in 1% and 0%).
Improved Outcomes in Marrow Graft Recipients
In multivariate analysis adjusting for recipient and donor characteristics, 3-year overall survival was significantly increased in marrow graft recipients with donors who had greater than median levels of plasmacytoid dendritic cells (56% vs 35%, P = .025), naive CD8-positive T cells (56% vs 37%, P = .012), and naive CD4-positive T cells (55% vs 37%, P = .009).
Marrow graft recipients who received higher vs lower than median levels (0.3 × 106 cells/kg) of plasmacytoid dendritic cells also had significantly improved disease-free survival (P = .02), reduced treatment-related mortality (P = .01), and significantly fewer deaths resulting from graft rejection and graft-vs-host disease, with no differences in grade II to IV or III to IV or chronic graft-vs-host disease or relapse being observed.
Marrow graft recipients who received higher vs lower than median levels of naïve T cells (1.3 × 106 cells/kg for CD8-positive T cells, 2.6 × 106 cells/kg for CD4-positive T cells) also had significantly improved disease-free survival (P = .01), reduced treatment-related mortality (P = .04), and reduced grade III or IV graft-vs-host disease, with no differences in grade II to IV or chronic graft-vs-host disease or relapse being observed.
No Associations for Peripheral Blood Grafts
Analysis of peripheral blood grafts did not identify a donor cell subset significantly associated with overall survival, relapse, or graft-vs-host disease.
The investigators concluded, “Donor immune cells in [bone marrow] but not [peripheral blood] stem-cell grafts were associated with survival after unrelated-donor allogeneic hematopoietic stem-cell transplantation. The biologic activity of donor immune cells in allogeneic transplantation varied between graft sources. Donor grafts with more [bone marrow]–derived [naive T cells] and [plasmacytoid dendritic cells] favorably regulated post-transplantation immunity in allogeneic hematopoietic stem-cell transplantation.”
Edmund K. Waller, MD, of Emory University, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by the National Heart, Lung, and Blood Institute, National Cancer Institute, Department of the Navy, and National Marrow Donor Program. The study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
