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.
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.
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
Qin
Q
Li
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
Lalit
L
Rane
Division of Therapeutic Immunology, Labmed, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Thomas
T
Poiret
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
Jiezhi
J
Zou
Department of Oncology-Pathology (OnkPat), Karolinska University Hospital, Stockholm, Sweden.
Isabelle
I
Magalhaes
Public Health Agency, Solna, Sweden.
Raija
R
Ahmed
Division of Neuropathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Ziming
Z
Du
Department of Immunobiology and Internal Medicine, Yale University, New Haven, CT, USA.
Nalini
N
Vudattu
Division of Therapeutic Immunology, Labmed, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Qingda
Q
Meng
Department of Clinical Science, Intervention an Technology (CLINTECH), Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Åsa
Å
Gustafsson-Jernberg
Department of Clinical Science, Intervention an Technology (CLINTECH), Karolinska University Hospital, Huddinge, Stockholm, Sweden.|Department of Pediatrics, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Jacek
J
Winiarski
Division of Therapeutic Immunology, Labmed, Karolinska University Hospital, Huddinge, Stockholm, Sweden.|Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Olle
O
Ringdén
Division of Therapeutic Immunology, Labmed, Karolinska University Hospital, Huddinge, Stockholm, Sweden.|Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Markus
M
Maeurer
Division of Therapeutic Immunology, Labmed, Karolinska University Hospital, Huddinge, Stockholm, Sweden.|Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Mats
M
Remberger
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
Ingemar
I
Ernberg
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000150:complications / Q000821:virology*; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications / Q000175:diagnosis* / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000150:complications / Q000628:therapy*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult
D004279:DNA, Viral
EBV DNA-load; Immune response; Immunity; Immunology and Microbiology Section; T-cell phenotype; aGVHD; stem cell transplantation; total body irradiation