TY - JOUR
T1 - Granulocyte Colony-Stimulating Factor-Mobilized Allografts Contain Activated Immune Cell Subsets Associated with Risk of Acute and Chronic Graft-versus-Host Disease
AU - Vasu, Sumithira
AU - Geyer, Susan
AU - Bingman, Anissa
AU - Auletta, Jeffery J.
AU - Jaglowski, Samantha
AU - Elder, Pat
AU - Donnell, Lynn O.
AU - Bradbury, Hillary
AU - Kitzler, Rhonda
AU - Andritsos, Leslie
AU - Blum, William
AU - Klisovic, Rebecca
AU - Penza, Sam
AU - Efebera, Yvonne
AU - Hofmeister, Craig
AU - Benson, Don M.
AU - Muthusamy, Natarajan
AU - Lozanski, Gerard
AU - Devine, Steven M.
N1 - Publisher Copyright:
© 2016 American Society for Blood and Marrow Transplantation.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - Acute GVHD
KW - Allograft content of NK cells
KW - Chronic GVHD
KW - HLA-DR CD3 cells
KW - Leukemic relapse
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U2 - 10.1016/j.bbmt.2015.12.015
DO - 10.1016/j.bbmt.2015.12.015
M3 - Article
C2 - 26743340
AN - SCOPUS:84960491288
SN - 1083-8791
VL - 22
SP - 658
EP - 668
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 4
ER -