Low Counts of Plasmacytoid Dendritic Cells after Engraftment Are Associated with High Early Mortality after Allogeneic Stem Cell Transplantation

Abstract Dendritic cells (DCs) are antigen-presenting cells that drive immune responses and tolerance and are divided in different subsets: myeloid DCs (mDCs: lineage−; HLA-DR+, 11c+), plasmacytoid dendritic cells (pDCs: HLA-DR+, CD123+), and monocyte-derived DCs (moDC: lineage−, 11c+, 16+). After h...

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Published in:	Biology of blood and marrow transplantation Vol. 21; no. 7; pp. 1223 - 1229
Main Authors:	Gonçalves, Matheus Vescovi, Yamamoto, Mihoko, Kimura, Eliza Yurico Sugano, Colturato, Vergílio Antônio Rensi, de Souza, Mair Pedro, Mauad, Marcos, Ikoma, Maura Valerio, Novis, Yana, Rocha, Vanderson, Ginani, Valeria Cortez, Wanderley de Oliveira Felix, Olga Margareth, Seber, Adriana, Kerbauy, Fabio Rodrigues, Hamerschlak, Nelson, Orfao, Alberto, Rodrigues, Celso Arrais
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-07-2015
Subjects:	Acute Disease Adolescent Adult Aged Bone Marrow Transplantation - adverse effects Cell Count Cell Lineage - immunology Child Child, Preschool Cord Blood Stem Cell Transplantation - adverse effects Dendritic cells Dendritic Cells - classification Dendritic Cells - immunology Dendritic Cells - pathology Female Graft vs Host Disease - drug therapy Graft vs Host Disease - etiology Graft vs Host Disease - immunology Graft vs Host Disease - mortality Graft-versus-host disease Hematologic Neoplasms - immunology Hematologic Neoplasms - mortality Hematologic Neoplasms - pathology Hematologic Neoplasms - therapy Hematology, Oncology and Palliative Medicine Hematopoietic Stem Cell Transplantation - adverse effects Humans Immune recovery Immunosuppressive Agents - therapeutic use Infant Male Middle Aged Myeloablative Agonists - therapeutic use Nonrelapse mortality Siblings Survival Analysis Transplantation Transplantation Conditioning Transplantation, Homologous Unrelated Donors Graft-versus-host disease Transplantation Dendritic cells Immune recovery Nonrelapse mortality
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Summary:	Abstract Dendritic cells (DCs) are antigen-presenting cells that drive immune responses and tolerance and are divided in different subsets: myeloid DCs (mDCs: lineage−; HLA-DR+, 11c+), plasmacytoid dendritic cells (pDCs: HLA-DR+, CD123+), and monocyte-derived DCs (moDC: lineage−, 11c+, 16+). After hematopoietic stem cell transplantation (HSCT), low DC counts in the recipients' peripheral blood (PB) have been associated with worse outcomes, but the relevance of DC graft content remains unclear, and there are few data in the setting of unrelated donor HSCT. We evaluated the DC graft content and monitored DC recovery in PB from 111 HSCT recipients (median age, 17 years; range 1 to 74), who received bone marrow (46%), umbilical cord blood (32%), or PB (22%) from unrelated (81%) or related donors (19%). In 86 patients with sustained allogeneic recovery, patients with higher counts of all DC subsets (pDC, mDC, and moDC) 3 weeks after engraftment had lower incidence of nonrelapse mortality (NMR) and acute graft-versus-host disease (aGVHD) and better survival. pDC counts were associated with more striking results: patients with higher pDC counts had much lower incidences of NRM (3% versus 47%, P < .0001), lower incidence of aGVHD (24% versus 67%, P < .0001), and better overall survival (92% versus 45%, P < .0001). In contrast, higher pDC counts in the graft was associated with an increased risk of aGVHD (55% versus 26%, P = .02). Our results indicate that DC counts are closely correlated with HSCT outcomes and warrant further prospective evaluation and possible early therapeutic interventions to ameliorate severe aGVHD and decrease mortality.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1083-8791 1523-6536
DOI:	10.1016/j.bbmt.2015.03.010