Very High Seroprevalence of CMV and EBV Among a Large Series of Patients with Hematological Malignancies at a Tertiary Care Center in Saudi Arabia - a Case for Investigating Cooperativity of Viruses in Carcinogenesis?

Background: Hematology practice in developing countries has some unique issues including a higher prevalence of infectious disease markers. Epstein-Barr virus (EBV) is an oncogenic virus and implicated in Burkitt's lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma and leiomyosarcoma in the immunocompromised (Ito Y et al. 2009). Cytomegalovirus (CMV) infection/reactivation in patients with hematological malignancies causes serious morbidity and mortality. Saudi Arabia is a high income rapidly developing country, but seroprevalence of CMV and EBV is reportedly higher compared to developed countries (Ghazi 2002, Seale et al., 2006, Joseph et al., 2005). EBV & CMV co-infection is not infrequent & occurs most commonly in the immunocompromised host. A significantly higher prevalence of antibodies (Abs) against CMV & EBV in some disease groups compared to controls has been reported from the same communities (Ocak et al., 2006, Al-Hakami et al., 2016). Interestingly, CMV disease occurrence in sibling donor hematopoietic stem cell transplant (HSCT) is infrequent in our area in spite of the occurrence of CMV reactivations (Aljurf et al., 2009, Saovic et al., 1999). Hence, knowledge of seroprevalence of these viruses in hematological malignancies may be helpful in strategic planning for transplants & transfusions. It may help in establishing any plausible etiological linkage with certain hematological malignancies. Methods: We retrospectively examined the records of adult patients (>14 years) with hematological malignancies for CMV and EBV status (IgG and IgM Abs by chemiluminescence immunoassay). We identified 2,007 patients (1104 males and 903 females) and grouped them according to gender along with broad hematological malignancy categories (Table 1). We tried to establish if any disease category had extraordinary seropositivity for CMV (IgG ≥20 U/ml) or EBV (IgG ≥12 U/ml). We also studied the prevalence of IgM Abs in those tested positive for IgG Abs. Results: Of 2,007 patients (males significantly more than females, p = 0.001), age range 14-93 year (mean 47.2), 503 underwent testing for CMV status and 520 for EBV. Among these tested patients, there was no significant gender difference as 96.1% males were CMV positive, and 95.4% females were CMV positive. On the other hand, 96.9% males were EBV IgG Abs positive compared to 92.5% of females, which was 2.56 (95% CI; 1.12 - 5.96) times more likely to be positive in the studied male patien