Research Papers: Immunology:
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
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Qin Li1, Lalit Rane1, Thomas Poiret2, Jiezhi Zou1, Isabelle Magalhaes3, Raija Ahmed4, Ziming Du5, Nalini Vudattu6, Qingda Meng2, Åsa Gustafsson-Jernberg7, Jacek Winiarski7,9, Olle Ringdén2,8, Markus Maeurer2,8, Mats Remberger2,8 and Ingemar Ernberg1
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 Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Stockholm, Sweden
9 Department of Pediatrics, Karolinska University Hospital, Huddinge, Stockholm, Sweden
Ingemar Ernberg, email:
Keywords: stem cell transplantation, EBV DNA-load, T-cell phenotype, total body irradiation, aGVHD, Immunology and Microbiology Section, Immune response, Immunity
Received: March 04, 2016 Accepted: April 11, 2016 Published: April 19, 2016
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 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.
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