title: Granulocyte Colony-Stimulating Factor-Mobilized Allografts Contain Activated Immune Cell Subsets Associated with Risk of Acute and Chronic Graft-versus-Host Disease.
abstract: We defined associations among immune cell subsets in granulocyte colony-stimulating factor (G-CSF)-mobilized allografts and clinical outcomes after allogeneic hematopoietic cell transplantation (alloHCT). Fresh peripheral blood stem cell (PBSC) aliquots from 238 G-CSF-mobilized allografts were extensively characterized by immunophenotype. Subset-specific transplanted cells were correlated with acute graft-versus-host disease (aGVHD), chronic GVHD (cGVHD), malignant disease relapse, nonrelapse mortality, and overall survival. Of 238 assessable alloHCT recipients, 185 patients (78%) received reduced-intensity conditioning and 152 (64%) antithymocyte globulin-based serotherapy. Incidences of aGVHD and cGVHD were 58% and 48%, respectively. Median follow-up was 21 months (range, 1.4 to 41.1). In multivariable analyses adjusted for relevant clinical factors, allograft activated natural killer (NK) cells (CD56(+)CD16(+)CD69(+)CD158b(+)) were associated with a significantly lower risk of aGVHD (P = .0016; HR, .51; 95% confidence interval, .33 to .78), whereas late-activated HLA-DR(+) CD3(+) cells were associated with significantly higher aGVHD (P < .0005; HR, 2.31; 95% confidence interval, 1.55 to 3.43). In a subgroup of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), receipt of an allograft from an older donor (≥40 years) was associated with a higher incidence of relapse (P = .0042; HR, 2.99); allograft content of early activated CD3(+) cells (CD3(+)CD69(+); P = .0024; HR, .4) and NKT cells (CD3(+)CD56(+); P = .0006; HR, .54) were associated with a lower incidence of relapse. Presence of HLA-Bw4-80Ile(+) genotype was associated with lower relapse incidence. In conclusion, activated NK cells within PBSC allografts associate with lower aGVHD risk, whereas HLA-DR(+) T cells associate with higher aGVHD and cGVHD risk. NKT cells and early activated T cells are associated with lower relapse risk in AML and MDS patients. These findings may have implications in therapeutic targeting of select populations in the allograft to minimize incidence of GVHD.
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Sumithira
authors.initials: S
authors.lastname: Vasu
authors.affiliation: Department of Epidemiology and Biostatistics, University of South Florida, Tampa, Florida.
authors.forename: Susan
authors.initials: S
authors.lastname: Geyer
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Anissa
authors.initials: A
authors.lastname: Bingman
authors.affiliation: Host Defense Program, Nationwide Children's Hospital, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Jeffery J
authors.initials: JJ
authors.lastname: Auletta
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Samantha
authors.initials: S
authors.lastname: Jaglowski
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Pat
authors.initials: P
authors.lastname: Elder
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Lynn C
authors.initials: LC
authors.lastname: O'Donnell
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Hillary
authors.initials: H
authors.lastname: Bradbury
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, Ohio.
authors.forename: Rhonda
authors.initials: R
authors.lastname: Kitzler
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Leslie
authors.initials: L
authors.lastname: Andritsos
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: William
authors.initials: W
authors.lastname: Blum
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Klisovic
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Sam
authors.initials: S
authors.lastname: Penza
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Efebera
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Craig
authors.initials: C
authors.lastname: Hofmeister
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors.forename: Don M
authors.initials: DM
authors.lastname: Benson
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio; Department of Epidemiology and Biostatistics, University of South Florida, Tampa, Florida.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Muthusamy
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, Ohio.
authors.forename: Gerard
authors.initials: G
authors.lastname: Lozanski
authors.affiliation: Division of Hematology, Department of Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, Ohio. Electronic address: vijigopi24@gmail.com.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Devine
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D011247:Pregnancy; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016559:Tacrolimus / Q000627:therapeutic use; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D016559:Tacrolimus; D008727:Methotrexate
keywords: Acute GVHD; Allograft content of NK cells; Chronic GVHD; HLA-DR(+) CD3(+) cells; Leukemic relapse