Faculty Collaboration Database

Granulocyte Colony-Stimulating Factor-Mobilized Allografts Contain Activated Immune Cell Subsets Associated with Risk of Acute and Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant 2016 Apr;22(4):658-668

Date

01/09/2016

Pubmed ID

26743340

DOI

10.1016/j.bbmt.2015.12.015

Scopus ID

2-s2.0-84960491288 (requires institutional sign-in at Scopus site)   18 Citations

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.

Author List

Vasu S, Geyer S, Bingman A, Auletta JJ, Jaglowski S, Elder P, O'Donnell LC, Bradbury H, Kitzler R, Andritsos L, Blum W, Klisovic R, Penza S, Efebera Y, Hofmeister C, Benson DM, Muthusamy N, Lozanski G, Devine SM

Author

Samantha M. Jaglowski MD, MPH Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Antilymphocyte Serum
Female
Graft vs Host Disease
Granulocyte Colony-Stimulating Factor
Hematologic Neoplasms
Hematopoietic Stem Cell Mobilization
Hematopoietic Stem Cell Transplantation
Humans
Immunosuppressive Agents
Killer Cells, Natural
Male
Methotrexate
Middle Aged
Peripheral Blood Stem Cell Transplantation
Pregnancy
T-Lymphocytes
Tacrolimus
Transplantation Conditioning
Transplantation, Homologous