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Improved survival after transplantation of more donor plasmacytoid dendritic or naïve T cells from unrelated-donor marrow grafts: results from BMTCTN 0201. J Clin Oncol 2014 Aug 01;32(22):2365-72 PMID: 24982459 PMCID: PMC4180368

Pubmed ID

24982459

DOI

10.1200/JCO.2013.54.4577

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 naïve 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, naïve CD8(+) T cells (CD8Tns), or naïve 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.

Author List

Waller EK, Logan BR, Harris WA, Devine SM, Porter DL, Mineishi S, McCarty JM, Gonzalez CE, Spitzer TR, Krijanovski OI, Linenberger ML, Woolfrey A, Howard A, Wu J, Confer DL, Anasetti C

Author

Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin




Scopus

2-s2.0-84905828126   39 Citations

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Bone Marrow Transplantation
Child
Child, Preschool
Dendritic Cells
Female
Humans
Infant
Infant, Newborn
Leukemia
Male
Middle Aged
Myelodysplastic Syndromes
Myeloproliferative Disorders
Primary Myelofibrosis
Survival Analysis
Survival Rate
T-Lymphocytes
Unrelated Donors
Young Adult
jenkins-FCD Prod-331 a335b1a6d1e9c32173c9534e6f6ff51494143916