Background: Higher peak adenovirus (ADV) viral loads (VL) have correlated with higher mortality in allogeneic hematopoietic cell transplant (HCT) recipients. ADV viral dynamics may inform trial design of new treatment strategies. We examined the relationship between cumulative viral burden expressed as average area under the curve (AAUC) and mortality.
Methods: We identified 62 HCT at MSK monitored by plasma ADV qPCR (Viracor-Eurofins) who had >1 value of ADV VL ≥100 copies/mL <100 days post-HCT. AAUC was calculated as the sum of the area of trapezoids of AAUC VL (log10 copies/mL) divided by the duration (weeks) of viremia. AAUC was categorized into quartiles (Q). Survival was obtained by the Kaplan-Meier method at 16 weeks from onset of ADV. Cox proportional hazard models were used to evaluate the association between AAUC and mortality. Age, underlying disease, HLA match, stem cell source, ex-vivo T-cell depletion (TCD) and acute graft-versus-host disease (aGVHD) were included in the model.
Results: Of 62 patients, 24 (39%) were children, 40 (65%) had acute leukemia or myelodysplastic syndrome, 50 (81%) received myeloablative conditioning, 41(66%) received TCD HCT and 11 (18%) received cord blood allograft. 67% of children and 82% of adults had maximum ADV VL >1,000 copies/ml. The median maximum VL was 2.8 log10 copies/mL in Q1, 4.4 log10 copies/mL in Q2, 5.0 log10 copies/mL in Q3, 5.3 log10 copies/mL in Q4 respectively. Figure shows survival estimate by AAUC Q. Higher AAUC was associated with lower survival. After adjusting for covariates, AAUC (hazard ratio [HR] 1.9; 95% confidence interval [CI] 1.2 - 3.0, P=0.0065) were associated with mortality. Among other covariates, only aGVHD was associated with mortality (HR 11.7; 95% CI 1.4 - 98.9, P=0.049).
Conclusion: In this pilot study of 62 HCT recipients comprising of 66% TCD, the cumulative ADV burden was associated with mortality. Larger studies are needed to validate our findings and assess the impact of immune reconstitution and antiviral treatments on outcomes of ADV viremia.
Y. J. Lee,
M. A. Perales, None
S. Prockop, None
G. Papanicolaou, Chimerix: Consultant , Consulting fee , Research grant and Speaker honorarium .
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