Adenovirus and BK Virus Co-Infection in the Pediatric Recipient of Stem Cell Transplant with CMV Infection.
Authors: Hongeng Suradej , Watcharananan Siriorn , Anurathapan Usanarat , Piyatuctsanawong Wisutwadee , Pakakasama Samart , Sirachainan Nongnuch , Sirinavin Sayomporn , Chantratita Wasan 
Published: October 2019

Background: Viral infections are a common cause of complication following hemopoietic stem cell transplantation (HSCT). Cytomegalovirus (CMV) is known to be a concerning pathogen and most transplant centers have implemented CMV monitoring as a standard of care. With improvement of virological diagnostic methods, the role of other viruses including adenovirus (ADV) and polyomaviruses (PMV) as pathogens causing major infection are also increasingly appreciated, however, evidence to support routine monitoring of these viruses following HSCT is lacking. In addition, there is a paucity of data on the incidence of ADV and/or PMV co-infection in children who develop CMV infection following HSCT. The aim of this study was to uncover the incidence of CMV and ADV or PMV co-infection in pediatric recipients of allogeneic- HSCT and to correlate the finding with degree of CMV viremia.

Methods: We retrospectively performed Q-RT- PCR of ADV, BKV and JCV in 219 blood samples from 77 pediatric patients following allogeneic- HSCT, initially taken for quantitative real-time PCR of CMV (monthly post engraftment, as a routine CMV monitoring, or weekly if CMV syndrome was suspected). These patients were known to have varying degree of CMV viremia.We defined high graded, low to moderate graded and undetectable CMV viremia as CMV viral load > 10,000, 400-< 10,000 and < 400 copies/ml.The lower limit of viral load detection is 400 and 10 copies/ml for CMV and for ADV, BKV and JCV.

Results: Twenty-eight patients (36%) had CMV viremia, of which were high graded (peak viral load 32,000->100,000 copies/ml) in 13 patients (17%), in at least one moment of follow up. Twelve patients (15%) had ADV viremia, whereas 40 (52%) had BKV viremia. ADV and BKV viremia occurred in 3 (23%) and 10 (77%) of patients with high-graded CMV viremia and they were mostly high graded (ADV and BKV peak viral load 11,400–367,000 and 10–2,120 copies/ml). In patients with non-high graded CMV viremia, most of them had lower graded ADV and BKV viremia (peak viral load 1,830–14,800 and 10–441 copies/ml), except for one patient who had ADV viral load 3,140,000 copies/ml and BKV viral load of 10 copies/ml. Five patients (6.5%) had CMV, ADV and BKV co-viremia, which were most frequent in patients with high-graded CMV viremia (15%).Two patients (2.5%) had very low JCV viremia (viral load 10 and 13 copies/ml). See Table for summarized results.

Conclusion: In pediatric allogeneic HSCT, CMV, BKV and ADV infection is common. High-graded, BKV, ADV or BKV and ADV co-viremia occurred most frequently in patients with high-graded CMV viremia. Low-graded BKV and ADV viremia mostly occurred in patient without high-graded CMV viremia. JCV viremia was not common and occurred irrespective of CMV infection. From our study, monitoring of ADV and BKV should be considered in patients with high-graded CMV viremia following pediatric allogeneic HSCT.

CMV viral load (copies/ml) >10,000 400- <10,000 < 400 Number of patients (%) Total patients Cytomegalovirus 13(17%) 15(19%) 49(64%) 77(100%) Adenovirus 3(23%) 1(6%) 8(16%) 12(15%) BK virus 10(77%) 3(23%) 27(55%) 40(52%) JC virus 0 0 2(4%) 2(2.5%) Adenovirus and BK virus 2(15%) 1(6%) 2(4%) 5(6.5%)