Improved Survival After Transplantation of More Donor Plasmacytoid Dendritic or Naive T Cells from Unrelated-Donor Marrow Grafts: Results From BMTCTN 0201
08/2014
Journal Article
Authors:
Waller, E.K.;
Logan, B.R.;
Harris, W.A.;
Devine, S.M.;
Porter, D.L.;
Mineishi, S.;
McCarty, J.M.;
Gonzalez, C.E.;
Spitzer, T.R.;
Krijanovski, O.I.;
Linenberger, M.L.;
Woolfrey, A.;
Howard, A.;
Wu, J.;
Confer, D.L.;
Anasetti, C.
Secondary:
J Clin Oncol
Volume:
32
Pagination:
2365-2372
URL:
http://www.ncbi.nlm.nih.gov/pubmed/24982459
Keywords:
Bone Marrow Transplantation; Dendritic Cells; GVHD; Leukemia/therapy; Myelodysplastic Syndromes; Myeloproliferative Disorders; Primary Myelofibrosis; Survival Analysis; T-Lymphocytes; Unrelated Donors
Abstract:
PURPOSE: To characterize relationships between specific immune cell subsets in bone marrow (BM) or granulocyte colony-stimulating factor-mobilized peripheral blood (PB) stem cells collected from unrelated donors and clinical outcomes of patients undergoing transplantation in BMTCTN 0201. PATIENTS AND METHODS: Fresh aliquots of 161 BM and 147 PB stem-cell allografts from North American donors randomly assigned to donate BM or PB stem cells and numbers of transplanted cells were correlated with overall survival (OS), relapse, and graft-versus-host disease (GvHD). RESULTS: Patients with evaluable grafts were similar to all BMTCTN 0201 patients. The numbers of plasmacytoid dendritic cells (pDCs) and naive T cells (Tns) in BM allografts were independently associated with OS in multivariable analyses including recipient and donor characteristics, such as human leukocyte antigen mismatch, age, and use of antithymocyte globulin. BM recipients of > median number of pDCs, naive CD8(+) T cells (CD8Tns), or naive CD4(+) T cells (CD4Tns) had better 3-year OS (pDCs, 56% v 35%; P = .025; CD8Tns, 56% v 37%; P = .012; CD4Tns, 55% v 37%; P = .009). Transplantation of more BM Tns was associated with less grade 3 to 4 acute GvHD but similar rates of relapse. Transplantation of more BM pDCs was associated with fewer deaths resulting from GvHD or from graft rejection. Analysis of PB grafts did not identify a donor cell subset significantly associated with OS, relapse, or GvHD. CONCLUSION: Donor immune cells in BM but not PB 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 BM-derived Tns and pDCs favorably regulated post-transplantation immunity in allogeneic hematopoietic stem-cell transplantation.
