1411 - Risks and Outcomes of Adenovirus Disease in Pediatric HSCT Recipients –Comparison of Current Antiviral Treatment Options

Background: Adenovirus can cause multi-organ dysfunction in hematopoietic stem cell transplant recipients (SCTr). It accounts for 22% of infection-associated mortality in umbilical cord transplant recipients (UCTr). This study determines whether transplant characteristics are associated with risk of adenovirus disease (ADVd), and compares time to resolution of ADVd between patients who received antiviral therapy.

Methods: We conducted a retrospective single center cohort study of pediatric patients undergoing stem cell transplant at Duke University between 2005 and 2016. We identified cases of single end-organ and disseminated ADVd (2 or more organs) using a classification tool defined a priori.  We used a Cox proportional hazards (CPH) regression model to compare the hazard of ADVd between SCTr differing by type of transplant and type of conditioning regimen. We also used CPH to compare the hazard of time to resolution of ADVd between SCTr differing by absence or presence of antiviral therapy (cidofovir, brincidofovir or both).

Results: There are 830 subjects, including 93 subjects with ADVd post-SCT. UCTr had 3.30 times the hazard of developing ADVd compared to non-cord blood allogeneic transplants and 7.30 times the hazard compared to autologous transplants (Figure 1). No difference in hazard of ADVd was detected between patients who received myeloablative vs non-myeloablative conditioning. Twenty-seven percent of the subjects received antiviral therapy; these patients had higher mortality (38%). The majority (87%) of diseased subjects had resolution of disease. Subjects that did not receive antiviral therapy experienced earlier resolution of ADVd compared to subjects who received antiviral therapy even after adjusting for subjects with disseminated disease (HR (95% CI): 3.75 (1.57, 8.93), p=0.003). Subjects with single end organ disease had earlier resolution of ADVd compared to disseminated disease (HR (95% CI): 2.24 (1.22, 4.10), p=0.009).Figure 1a. Kaplan-Meier curve depicting survival free of adenovirus-disease for the first year post-HSCT by type of transplant.
Figure 1b. Kaplan-Meier curve depicting survival free of adenovirus-disease for the first year post-HSCT by type of conditioning regimen.


Conclusion: This is the first pediatric cohort study to report risk factors and clinical outcomes of ADVd, irrespective of ADV-DNAemia.  UCTr recipients have a higher hazard of ADVd compared to other SCTr. Contrary to previous reports studying ADV-DNAemia, our study noted an earlier resolution of ADVd in the absence of antiviral therapy.