Investigation of incidence and clinical importance of hhv-6 infections in pediatric stem cell transplant recipients and the effect of viral integration on diagnostic tests in Akdeniz University Hospital prospectively

The compromised immune system in stem cell transplant recipients (SCT), because of the administration of immunosuppressive drugs after SCT, make patients more susceptible and vulnerable for active infection. Active infection is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT), and are suggested to be associated with acute graft-versus-host disease (aGVHD), allograft rejections, and increased nonrelapse mortality.The active HHV-6 infections after transplantation, can cause viral hepatitis, fever, skin rash, delayed platelet and neutrophil engrafment, acute GVHD, allograft rejection. A better understanding of active HHV-6 infection after transplantation can reduce the incidence of complications that is associated with HHV-6 reactivation and paves the way for preventive and therapeutic options for HHV-6 infection. Although some studies have already been reported the HHV-6 active infection and clinical relation in adults, clinical results in children aren?t known exactly.In this study, we aimed to investigate the relationship between clinical findings and identify the risk factors for active HHV-6 infections by determining the pre-transplant serologic status and the frequency of the HHV-6 infection after transplantation.Thirty nine patients who had stem cell transplantation at Akdeniz University Faculty of Medicine pediatric stem cell transplant unit, between 06.10.2011 and 04. 06. 2012 with age ranging from 1 to 17 were included in this study.Pre-transplant HHV-6 lgG of 38 patients were studied from plasma samples. It was positive for 895 %, gray zone for 7.9% and negative for 2.6% of the patients.For 12 (30.8%) patients, at least one sample were positive for HHV-6 DNA. After transplantation, the first positive samples for HHV-6 DNA were between two to 42 days. HHV-6 DNA has found positive in 34.6% of 26 boys and 23.1 %13 girls.The serological positivity rate among HHV-6 DNA positive patients was 29.4%. Two of three patient with gray zone results for HHV-6 serology (66.7%) were positive for HHV-6 DNA. No infection was found in one patient with negative serology.In our study, the positivity for HHV-6 in mismatched and matched HLA recipients were 62.5 and 8.7% respectively. The patients who were incompatible with HLA, were more frequently positive for HHV-6. This finding was statistically significant (p=0.001).Ten of 39 (25.6%) patients had aGVHD. 33.3 % of the patients who had positive HHV-6 DNA, developed aGVHD. 6 of the 27 patients who had negative HHV-6 DNA had aGVHD. There was no significant correlation between the patients who had positive HHV-6 DNA and aGVHD (p>0.05).23.1% of all patients had cutaneous manifestations. Four of the 12 patients who had positive HHV-6 DNA had evidence of cutaneous manifestations. There was no significant relationship between cutaneous manifestations and HHV-6 DNA positivity.Fever was seen in 91.7% of patients who had positive HHV-6 DNA. 96.3% of the patients who had negative HHV-6 DNA, had fever in some periods. Only 1 patient (3.7%) didn?t have fever. There was no significant correlation between HHV-6 positivity and fever after transplantation (p>0.05).There was an increase of liver enzymes in 16 of 39 patients (41%). Liver enzymes were increased at 6 of 12 patients (50%) who had positive HHV-6 DNA and again liver enzymes were increased at 10 of 27 (37%) patients who had negative HHV-6 DNA. There was no significant relation between the patients who had positive HHV-6 DNA and post-transplant increased liver enzymes.Neutrophil engraftment was ranged from 10 to 89 days (mean, 20.60±16.50). The median time for neutrophil engraftment was 16 days. Platelet engraftment was ranged between 10 to 150 days (mean, 26.90±26.811) and the median time after transplantation was 17 days. Neutrophil and platelet engraftment wasn?t seen for 4 and 9 patients respectively. The mean engraftment time for neutrophils among 11 patients who had positive HHV-6 DNA, was 16.55 days. The mean time for neutrophils engraftment was 18.67 days among patients who had negative HHV-6 DNA.The mean engraftment time for platelet among 8 patients who had positive HHV-6 DNA, was 9.19 days. The mean time for platelet engraftment was 17.8 days among 22 patients who had negative HHV-6 DNA. There was no significant relation between the patients who had positive HHV-6 DNA and neutrophil and platelet engraftment.In our study, which included 39 patients, chromosomal integrated HHV-6 was not detected.As a result, in children, after stem cell transplantation, active HHV-6 infection is very common. For HHV-6 positivity after transplantation, HLA match between donor and recipient, and myeloablative therapy appears to be important risk factors. Skin rash, liver damage and fever can be caused by active HHV-6 infections after transplantation. More extensive studies are needed in order to understand the impact of chromosomal integrated HHV-6 on diagnostic tests.