Publications

BACKGROUND

Adenovirus (AdV) is a serious infection following hematopoietic cell transplantation (HCT). Little is known about AdV viral kinetics and optimal threshold for initiation of pre-emptive therapy.

METHODS

Single-center retrospective study of 16 consecutive adult HCT recipients with detectable AdV identified over a 5-year period.

RESULTS

Median time to AdV reactivation after HCT was 176 days (IQR 86-408). Nine patients received cidofovir, although 14/16 had no tissue-invasive disease. Among treated patients, median duration of viremia was shorter when initiating treatment at viral loads < 10,000 copies/ml (28 vs. 52 days). All-cause mortality in this cohort was 44%. All six patients (five of which were untreated) with peak viral loads < 10,000 copies/ml survived; whereas only 30% (3/10) of patients with peak viral loads greater than this threshold survived, despite most (n = 8; 80%) of them receiving cidofovir (P = .01). Three-month survival following diagnosis of AdV viremia was significantly lower with peak viremia > 10,000 copies/ml (100 vs. 17%; P = .005).

CONCLUSION

AdV is associated with high all-cause mortality, especially for viremia > 10,000 copies/ml. Delaying therapy until viremia reaches AdV levels ≥10,000 copies/ml was associated with more protracted infection and poor outcomes. Larger studies are needed.

Cytogenetic and molecular abnormalities are known to influence post-transplant outcomes in acute myeloid leukemia (AML) but data assessing the prognostic value of combined genetic models in the HCT setting are limited. We developed an adapted European LeukemiaNet (aELN) risk classification based on available genetic data reported to the Center for International Blood and Marrow Transplant Research, to predict post-transplant outcomes in 2289 adult AML patients transplanted in first remission, between 2013 and 2017. Patients were stratified according to aELN into three groups: favorable (Fav, N = 181), intermediate (IM, N = 1185), and adverse (Adv, N = 923). Univariate analysis demonstrated significant differences in 2-year overall survival (OS) (Fav: 67.7%, IM: 64.9% and Adv: 53.9%; p < 0.001); disease-free survival (DFS) (Fav: 57.8%, IM: 55.5% and Adv: 45.3; p < 0.001) and relapse (Fav: 28%, IM: 27.5% and Adv: 37.5%; p < 0.001). Multivariate analysis (MVA) revealed no differences in outcomes between the Fav and IM groups, thus they were combined. On MVA, patients in the Adv risk group had the highest risk of relapse (HR 1.47 p ≤ 0.001) and inferior DFS (HR 1.35 p < 0.001) and OS (HR 1.39 p < 0.001), even using myeloablative conditioning or in those without the pre-HCT measurable-residual disease. Novel approaches to mitigate relapse in this high-risk group are urgently needed.