Adenovirus Isolation Post Blood and Marrow Transplant (BMT) in Australia and New Zealand- Results of a 4 Year Clinical Multi -Institutional Prospective Cohort Study.

Adenovirus (AdV) infection is an important cause of morbidity and mortality post BMT in both children and adults. The incidence of AdV in retrospective or single-centre prospective studies is reported between 4.9% and 41%. There are no published multi-institutional prospective clinical studies. We conducted a prospective cohort study from January 2001 to December 2004 in Australia and New Zealand for allogeneic and autologous BMT in children and adults, to find the incidence of AdV and disease post BMT and confirm risk factors for developing AdV. The 37 centres involved in the study completed a brief questionnaire every month to capture all recognized cases of AdV, and were periodically contacted to collect detailed data on patients who had AdV post transplant. The centres did not change their current practice of surveillance for AdV for this study. No centres were prospectively monitoring for adenoviraemia by polymerase chain reaction (PCR) in blood. We found an overall incidence of AdV disease or infection of 52/3468 (1.5%; 95% Confidence Interval [CI] 1.1 to 2.0), with 46/596, (7.7%; CI 5.7 to 10.2) in the paediatric population and 6/2872 (0.21%; CI 0.1 to 0.45) in the adult population. Although only 596/3468 (17%) of transplants were performed in children, 48% (CI 39 to 69) of all patients with AdV infection were 5 years of age or under. Using the established criteria1 of 52 patients with AdV infection, 14 had definite adenoviral disease and 27 probable adenoviral disease. Four (7.6%) patients died of adenovirus, two of multi-organ failure, one of liver failure and one of pneumonitis. There was a greater risk of developing AdV with an allogeneic transplant than an autologous transplant (RR 9.48, CI 4.2 to 20.9 p<0.001). In autologous transplants none of 1795 adults and only 7 of the 272 children had AdV. Children who had an allogeneic transplant with a T cell depleted graft were at greater risk of developing AdV than those with a T cell replete graft (RR 2.2, CI 1.20 to 4.1, p=0.02) as were those who had an unrelated compared to a related donor (RR 1.99, CI 1.02 to 3.85, p=0.05). Unrelated cord BMT compared to other unrelated transplants was not a statistically significant risk factor for developing AdV in this study (RR 1.1 CI 0.55 to 2.14 p = 0.98). The median day of detection of an AdV isolate for all patients was day 38 post transplant. However, there was a biphasic pattern, with 23.4% of all patients having the first AdV isolate identified greater than Day 100. 38.5% (CI 25.3– 53.0) of patients had isolation of AdV in more than one site. The most common site of an isolate was the gastrointestinal tract in 71% of patients, followed by positive blood PCR in 25%. 31 out of the 52 patients with AdV had another virus isolated apart from AdV; in 15 out of these 31 patients this virus was CMV, either reactivation or CMV disease. This prospective population-based study confirms the importance of AdV in BMT, particularly in paediatric T cell depleted unrelated donor BMT and highlights the occurrence of AdV infection greater than 100 days after transplant.