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Oncotarget. 2016 May 24;7(21):30230-40. doi: 10.18632/oncotarget.8803.

Both high and low levels of cellular Epstein-Barr virus DNA in blood identify failure after hematologic stem cell transplantation in conjunction with acute GVHD and type of conditioning.

Author information

1
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
2
Division of Therapeutic Immunology, Labmed, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
3
Department of Oncology-Pathology (OnkPat), Karolinska University Hospital, Stockholm, Sweden.
4
Public Health Agency, Solna, Sweden.
5
Division of Neuropathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
6
Department of Immunobiology and Internal Medicine, Yale University, New Haven, CT, USA.
7
Department of Clinical Science, Intervention an Technology (CLINTECH), Karolinska University Hospital, Huddinge, Stockholm, Sweden.
8
Department of Pediatrics, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
9
Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Stockholm, Sweden.

Abstract

The level of Epstein-Barr virus DNA in blood has proven to be a biomarker with some predictive value in allogeneic hematopoietic stem cell transplantation patients (HSCT). We evaluated the impact of EBV load on survival of 51 patients (32M/19F, median age: 32 years, from < 1 to 68 years old), who had received HSCT for different types of malignancies (49 cases) or non-malignancies (2 cases). The overall survival [1]was compared between patients with extreme and moderate cell bound EBV DNA levels. Different sources of stem-cells (peripheral blood stem, n = 39; bone marrow, n = 9; or umbilical cord blood, n = 3) were used. Twenty patients received reduced-intensity conditioning regimen while the other 31 received myeloablative conditioning. Patients with high or very low level of cell bound EBV-DNA levels had a shorter OS than those with moderate EBV load: OS at 5 years was 67% vs 90% (p < 0.03). There was a conspicuous relationship between EBV load and the reconstitution dynamics of total and EBV-specific T cells, CD4+ and CD4- CD8- (double negative) T cells in the few patients where it was analyzed. This was not statistically significant. Two other factors were associated to early mortality in addition to high or low EBV load: acute GVHD II-IV (p < 0.02) and pre-transplant conditioning with total body irradiation (TBI) ≥6 Gy, (p < 0.03). All the patients meeting all three criteria died within two years after transplantation. This points to a subgroup of HSCT patients which deserve special attention with improvement of future, personalized treatment.

KEYWORDS:

EBV DNA-load; Immune response; Immunity; Immunology and Microbiology Section; T-cell phenotype; aGVHD; stem cell transplantation; total body irradiation

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