Improved Survival After Transplantation of More Donor Plasmacytoid Dendritic or Naive T Cells From Unrelated-Donor Marrow Grafts: Results From BMTCTN 0201

• Type of Material: Article
• Authors: Edmund Waller, Emory University; Brent R. Logan, Medical College of Wisconsin; Wayne A. C. Harris, Emory University; Steven M. Devine, Ohio State University; David L. Porter, University of Pennsylvania; Shin Mineishi, University of Alabama Birmingham; John M. McCarty, Virginia Commonwealth University; Corina E. Gonzalez, Georgetown University Hospital; Thomas R. Spitzer, Massachusetts General Hospital; Oleg I. Krijanovski, Sutter East Bay Medical Foundation; Michael L. Linenberger, Fred Hutchinson Cancer Research Center; Ann Woolfrey, Fred Hutchinson Cancer Research Center; Alan Howard, National Marrow Donor Program; Juan Wu, Emmes Corporation; Dennis L. Confer, National Marrow Donor Program; Claudio Anasetti, University of South Florida
• Language: English
• Date: 2014-08-01
• Publisher: AMER SOC CLINICAL ONCOLOGY
• Publication Version: Final Published Version
• Copyright Statement: © 2014 by American Society of Clinical Oncology.
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.2013.54.4577
• Title of Journal or Parent Work: JOURNAL OF CLINICAL ONCOLOGY
• Volume: 32
• Issue: 22
• Start Page: 2365
• End Page: U124
• Grant/Funding Information: Supported by Grant No. U10HL069294 from the National Heart, Lung, and Blood Institute; by the National Cancer Institute, Department of the Navy, Office of Naval Research, and National Marrow Donor Program; and by the German Bone Marrow Donor Center (enrollment support).
• Keywords: INDUCTION; INDOLEAMINE 2,3-DIOXYGENASE; VERSUS-HOST-DISEASE; Life Sciences & Biomedicine; MOUSE; MOLECULES; PERSIST; CCR9; BONE-MARROW; IMMUNITY; Oncology; LEUKEMIA; Science & Technology
• Research Categories: Health Sciences, Immunology; Health Sciences, Oncology

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.