Kinetics of immune cell reconstitution predict survival in allogeneic bone marrow and G-CSF-mobilized stem cell transplantation

• Type of Material: Article
• Authors: Edmund K Waller, Emory University; Brent R. Logan, Medical College of Wisconsin; Mingwei Fei, Medical College of Wisconsin; Stephanie J. Lee, University of Washington; Dennis Confer, National Marrow Donor Program; Alan Howard, National Marrow Donor Program; Shanmuganathan Chandrakasan, Emory University; Claudio Anasetti, Moffitt Cancer Center; Shanelle M. Fernando, Emory University; Cynthia Giver, Emory University
• Language: English
• Date: 2019-01-01
• Publisher: American Society of Hematology: Blood Advances
• Publication Version: Final Published Version
• Copyright Statement: © 2019 by The American Society of Hematology.
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2018029892
• Title of Journal or Parent Work: Blood Advances
• ISSN: 2473-9529
• Volume: 3
• Issue: 15
• Start Page: 2250
• End Page: 2263
• Grant/Funding Information: Enrollment support was provided by DKMS Germany.; The Department of the Navy, Office of Naval Research, and the National Marrow Donor Program also provided support for the BMT CTN 0201 study.; This work was supported by grants 1R01CA188523-01A1 (E.K.W.) and U10HL069294 from the National Cancer Institute and National Heart, Lung, and Blood Institute, National Institutes of Health, which support the Blood and Marrow Transplant Clinical Trials Network that sponsored the clinical trial.
• Keywords: G-CSF; immune reconstitution; bone marrow transplantation; unrelated donor; blood T-cells; mobilized grafts
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Biostatistics

Abstract

The clinical utility of monitoring immune reconstitution after allotransplant was evaluated using data from Blood and Marrow Transplant Clinical Trials Network BMT CTN 0201 (NCT00075816), a multicenter randomized study of unrelated donor bone marrow (BM) vs granulocyte colony-stimulating factor (G-CSF)-mobilized blood stem cell (G-PB) grafts. Among 410 patients with posttransplant flow cytometry measurements of immune cell subsets, recipients of G-PB grafts had faster T-cell reconstitution than BM recipients, including more naive CD4+ T cells and T-cell receptor excision circle-positive CD41 and CD8+ T cells at 3 months, consistent with better thymic function. Faster reconstitution of CD4+ T cells and naive CD4+ T cells at 1 month and CD8+ T cells at 3 months predicted more chronic graft-versus-host disease (GVHD) but better survival in G-PB recipients, but consistent associations of T-cell amounts with GVHD or survival were not seen in BM recipients. In contrast, a higher number of classical dendritic cells (cDCs) in blood samples at 3 months predicted better survival in BM recipients. Functional T-cell immunity measured in vitro by cytokine secretion in response to stimulation with cytomegalovirus peptides was similar when comparing blood samples from BM and G-PB recipients, but the degree to which acute GVHD suppressed immune reconstitution varied according to graft source. BM, but not G-PB, recipients with a history of grades 2-4 acute GVHD had lower numbers of B cells, plasmacytoid dendritic cells, and cDCs at 3 months. Thus, early measurements of T-cell reconstitution are predictive cellular biomarkers for long-term survival and response to GVHD therapy in G-PB recipients, whereas more robust DC reconstitution predicted better survival in BM recipients.