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

Qin Li, Lalit Rane, Thomas Poiret, Jiezhi Zou, Isabelle Magalhaes, Raija Ahmed, Ziming Du, Nalini Vudattu, Qingda Meng, Åsa Gustafsson-Jernberg, Jacek Winiarski, Olle Ringdén, Markus Maeurer, Mats Remberger and Ingemar Ernberg _

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Oncotarget. 2016; 7:30230-30240. https://doi.org/10.18632/oncotarget.8803

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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

Correspondence to:

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 [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.

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