Clinical value of plasma and peripheral blood mononuclear cells Epstein–Barr Virus DNA dynamics on prognosis of allogeneic stem cell transplantation
The application of intracellular and extracellular Epstein–Barr virus (EBV) DNA in allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been poorly characterized. We conducted a combined prospective-retrospective study of 300 patients who underwent allo-HSCT between 2016 to 2019 in our...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.980113/full |
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| author | Xi Zhou Xuan Lu Jing He Ziwei Xu Qian Li Pian Ye Zhaodong Zhong Wei Shi Han Yan Yong You Yu Hu Huafang Wang |
| author_facet | Xi Zhou Xuan Lu Jing He Ziwei Xu Qian Li Pian Ye Zhaodong Zhong Wei Shi Han Yan Yong You Yu Hu Huafang Wang |
| author_sort | Xi Zhou |
| collection | DOAJ |
| description | The application of intracellular and extracellular Epstein–Barr virus (EBV) DNA in allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been poorly characterized. We conducted a combined prospective-retrospective study of 300 patients who underwent allo-HSCT between 2016 to 2019 in our center and monitored for EBV DNA within the first year after HSCT. Combining the optimal cut-off value of EBV DNA load (7.3×104 copies/106 cells) in peripheral blood mononuclear cells (PBMCs) and qualitative detection in plasma (400 copies/mL) allowed for the better differentiation of EBV-related posttransplant lymphoproliferative disorders (EBV-PTLD), with increased sensitivity (100%) and specificity (86%), and provided the effective risk stratification of EBV DNA level according to their impact on transplant outcomes. By multivariate analysis, patients with intermediate-level of EBV DNA load (low EBV DNA load in PBMCs or high load in PBMCs but negative in plasma) was associated with superior overall survival (HR 1.92, 95% CI 1.03-3.57, p=0.039) and lower transplant-related mortality (HR 3.35, 95% CI 1.31-8.58, p=0.012) compared to those with high-level (high load in PBMCs and positive in plasma). Notably, high EBV-level group had poor reconstitution of CD4+ and CD8+T cells, and both low and high EBV-level groups showed abnormally increase in IL-10 level within one year. Additionally, patients with peak EBV DNA load in PBMCs during 3-12 months had a higher incidence of chronic graft versus host disease (GVHD) than those within 3 months post transplantation (17.4% vs 13.7%, p=0.029). Collectively, EBV DNA in PBMCs can synergistically predict the risk of EBV-PTLD and GVHD. The intermediate-level of EBV DNA presented in plasma and PBMCs might contribute to a better reconstitution of T cells associated with favorable prognosis of allo-HSCT. |
| first_indexed | 2024-04-11T09:48:52Z |
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| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-11T09:48:52Z |
| publishDate | 2022-09-01 |
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| spelling | doaj.art-9ee95798e5384793857aa9ac5a1085f62022-12-22T04:30:53ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-09-011210.3389/fcimb.2022.980113980113Clinical value of plasma and peripheral blood mononuclear cells Epstein–Barr Virus DNA dynamics on prognosis of allogeneic stem cell transplantationXi Zhou0Xuan Lu1Jing He2Ziwei Xu3Qian Li4Pian Ye5Zhaodong Zhong6Wei Shi7Han Yan8Yong You9Yu Hu10Huafang Wang11Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaThe application of intracellular and extracellular Epstein–Barr virus (EBV) DNA in allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been poorly characterized. We conducted a combined prospective-retrospective study of 300 patients who underwent allo-HSCT between 2016 to 2019 in our center and monitored for EBV DNA within the first year after HSCT. Combining the optimal cut-off value of EBV DNA load (7.3×104 copies/106 cells) in peripheral blood mononuclear cells (PBMCs) and qualitative detection in plasma (400 copies/mL) allowed for the better differentiation of EBV-related posttransplant lymphoproliferative disorders (EBV-PTLD), with increased sensitivity (100%) and specificity (86%), and provided the effective risk stratification of EBV DNA level according to their impact on transplant outcomes. By multivariate analysis, patients with intermediate-level of EBV DNA load (low EBV DNA load in PBMCs or high load in PBMCs but negative in plasma) was associated with superior overall survival (HR 1.92, 95% CI 1.03-3.57, p=0.039) and lower transplant-related mortality (HR 3.35, 95% CI 1.31-8.58, p=0.012) compared to those with high-level (high load in PBMCs and positive in plasma). Notably, high EBV-level group had poor reconstitution of CD4+ and CD8+T cells, and both low and high EBV-level groups showed abnormally increase in IL-10 level within one year. Additionally, patients with peak EBV DNA load in PBMCs during 3-12 months had a higher incidence of chronic graft versus host disease (GVHD) than those within 3 months post transplantation (17.4% vs 13.7%, p=0.029). Collectively, EBV DNA in PBMCs can synergistically predict the risk of EBV-PTLD and GVHD. The intermediate-level of EBV DNA presented in plasma and PBMCs might contribute to a better reconstitution of T cells associated with favorable prognosis of allo-HSCT.https://www.frontiersin.org/articles/10.3389/fcimb.2022.980113/fullallo-HSCTEpstein-Barr virus DNAperipheral blood mononuclear cellsplasmaposttransplant lymphoproliferative disordersimmune reconstitution |
| spellingShingle | Xi Zhou Xuan Lu Jing He Ziwei Xu Qian Li Pian Ye Zhaodong Zhong Wei Shi Han Yan Yong You Yu Hu Huafang Wang Clinical value of plasma and peripheral blood mononuclear cells Epstein–Barr Virus DNA dynamics on prognosis of allogeneic stem cell transplantation Frontiers in Cellular and Infection Microbiology allo-HSCT Epstein-Barr virus DNA peripheral blood mononuclear cells plasma posttransplant lymphoproliferative disorders immune reconstitution |
| title | Clinical value of plasma and peripheral blood mononuclear cells Epstein–Barr Virus DNA dynamics on prognosis of allogeneic stem cell transplantation |
| title_full | Clinical value of plasma and peripheral blood mononuclear cells Epstein–Barr Virus DNA dynamics on prognosis of allogeneic stem cell transplantation |
| title_fullStr | Clinical value of plasma and peripheral blood mononuclear cells Epstein–Barr Virus DNA dynamics on prognosis of allogeneic stem cell transplantation |
| title_full_unstemmed | Clinical value of plasma and peripheral blood mononuclear cells Epstein–Barr Virus DNA dynamics on prognosis of allogeneic stem cell transplantation |
| title_short | Clinical value of plasma and peripheral blood mononuclear cells Epstein–Barr Virus DNA dynamics on prognosis of allogeneic stem cell transplantation |
| title_sort | clinical value of plasma and peripheral blood mononuclear cells epstein barr virus dna dynamics on prognosis of allogeneic stem cell transplantation |
| topic | allo-HSCT Epstein-Barr virus DNA peripheral blood mononuclear cells plasma posttransplant lymphoproliferative disorders immune reconstitution |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.980113/full |
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