Presence of Human Herpes Virus 6 (HHV6) in pediatric lymphomas: impact on clinical course and association with cytomegalovirus infection

Abstract

BackgroundActivation of herpes virus 6 (HHV6) has seen in Hodgkin's and non-Hodgkin's Lymphoma (HL&NHL) as a result of lymphoma associated immunosuppression. Multiple studies have suggested an association between both HHV6 and cytomegalovirus CMV for development of CMV disease affecting the pathogenesis of lymphoma. Therefore, this study investigated the frequency of HHV6, its impact on clinical manifestations of lymphoma and its possible association with risk for development of CMV infection in pediatric lymphoma patients.MethodsPresence of HHV6 DNA and CMV DNA was investigated by PCR assay in both WBC's and plasma samples from 50 patients diagnosed with HL or NHL. CMV antibody titer was also determined in sera obtained from each patient. Twenty apparently healthy siblings were used as a control group.ResultsIn a study group of 50 patients diagnosed with HL or NHL, 23/50 (46%) were found to be positive for herpes virus DNA (HHV6 or CMV) in WBC's or plasma by PCR assay and this was significantly higher than its presence in the pediatric control group 2/20 (10%) (p = 0.005). Ten out of these 23 (43%) were found to have active CMV infection. Fifty six percent of patients with CMV infection were found among NHL cases with B- subtype. The presence of both herpes viruses DNA was significantly associated with more frequent episodes of febrile neutropenia (median 3 episodes), absolute neutrophil count (< 0.8), lymphocytes (< 0.5), and low hemoglobin level (< 9.1), (p < 0.05).ConclusionThe presence of HHV6 can be considered as a predicting indicator of cellular immunosuppression preceding the onset of CMV infection which may result in a severe outcome among pediatric lymphoma patients.

Coreactivation of Human Herpesvirus 6 and Cytomegalovirus Is Associated With Worse Clinical Outcome in Critically Ill Adults*

“…This updated analysis of our initial study, which showed an association of CMV reactivation with prolonged hospitalization or death (12), advances understanding of particularly high-risk patient groups by considering HHV-6 in the models. Increased rates of adverse events in patients with co-reactivation of HHV-6 and CMV have been reported in other settings and are speculated to be due to mechanistic interactions between the two viruses (28, 29). …”

Prognostic Biomarkers for Hodgkin Lymphoma

“…The impact of most viruses on the pathogenesis of HL remains highly speculative. The presence of virus can be a consequence of immune suppression and subsequent virus reactivation in HL patients [21]. In agreement with this concept, presence of EBV in tumor cells has no significant impact on treatment results, but elevated levels of EBV DNA in the plasma at diagnosis correlates with inferior failure-free survival [22].…”

ecancermedicalscience

“…In the study by Sumiyoshi et al , HHV6 was found in about 50%–68% of patients with malignant lymphomas [25]. It can cause latent infection and subsequent reactivation during immunosuppression [26]. HHV was first reported as human lymphotropic virus, while further studies revealed its presence in some human tumours, especially paediatric lymphomas in association with CMV virus [26–28].…”

“…This virus is considered as an important opportunistic infection [26]. Presence of CMV in congenital tumours has also previously been reported, suggesting its role in some neonatal sarcomas’ progression [29].…”

“…There are some studies showing the presence of EBV or BK virus in some neonatal tumours, suggesting their role in tumour development or progression. EBV and CMV were detected in human lymphomas and neonatal sarcomas, respectively [26]. …”