کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2101345 1546255 2016 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Granulocyte Colony-Stimulating Factor–Mobilized Allografts Contain Activated Immune Cell Subsets Associated with Risk of Acute and Chronic Graft-versus-Host Disease
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Granulocyte Colony-Stimulating Factor–Mobilized Allografts Contain Activated Immune Cell Subsets Associated with Risk of Acute and Chronic Graft-versus-Host Disease
چکیده انگلیسی


• Activated T cell content in allografts is associated with higher incidences of aGVHD and cGVHD.
• Allograft activated NK cell content is associated with a lower incidence of aGVHD.
• In AML/MDS patients, early activated T and NKT cell content is associated with lower relapse.
• Presence of HLA-Bw4-80Ile+ genotype is associated with lower relapse-free survival.
• Unrelated donors were associated with a higher incidence of aGVHD and lower relapse.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 22, Issue 4, April 2016, Pages 658–668
نویسندگان
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