Prospective PCR Monitoring Reveals Adenovirus (ADV) Viremia Is Associated with a Significant Risk of Adv Disease in T-Cell Depleted and Cord Blood Allograft Recipients

Background: Adenovirus is an important cause of viral mortality in allogeneic hematopoietic stem cell transplantation. T-cell depletion (TCD) and the use of cord blood (CB) as a stem cell source are established risk factors for ADV viremia.  However, rates and outcomes of ADV are not well established in these populations. We prospectively monitored 104 adult recipients of TCD or CB allografts by qPCR for ADV to determine the rates of ADV viremia and disease to determine the utility of PCR surveillance in these high-risk patients.

Methods: This was a prospective observational study of adults transplanted 3/21/12-5/30/13 for treatment of hematologic malignancies at a single center. TCD was performed using CliniMacs® CD34+ cell selection and all CB transplantation (CBT) recipients received double-unit grafts. Patients were monitored for ADV by whole blood PCR assay (Viracor-IBT Laboratories) from 14 to at least 100 days post-transplant. ADV viremia was defined as ≥ 1 PCR positive (≥ lower limit detection). ADV disease was defined per European Group for Bone Marrow Transplantation guidelines. Treatment for ADV viremia was at the clinician’s discretion.

Results: 104 patients (median age 53 years, range 22-71) were transplanted including 73 (70%) TCD and 31 (30%) CB transplants. Patients received myeloablative, reduced-intensity, or non-myeloablative conditioning. 14 patients (8 TCD and 6 CBT recipients, 13% of cohort) had ADV viremia at a median onset of +73 days (range 12-119) and with a median viral load at first detection of 900 copies/mL (range 190-29,100). The median maximal viral load was 153,900 copies/mL. Five patients (5% of total cohort, 38% of viremic patients) developed ADV disease (3 colitis, 1 cystitis, 1 colitis with cystitis) at a median of 12 days from the first positive qPCR. (Three CBT patients with ADV disease received intravenous cidofovir and two TCD with ADV colitis received CMX001).  In addition, 5 patients (3 TCD and 2 CBT) were treated pre-emptively for ADV viremia (viral load > 10,000 copies/ml) with intravenous cidofovir.  Overall, 3 (21%) patients with ADV viremia died prior to day +100 (2 due to toxoplasmosis and 1 due to ADV and CMV).

Conclusions: While ADV viremia was infrequent (13%) in our high-risk cohort, ADV disease developed in approximately one-third of viremic patients. Overall, 10 out of 14 (76%) patients with ADV viremia received anti-viral therapy (5 for established disease and 5 pre-emptively). TCD and CB transplant recipients with ADV viremia are at high risk for disease. Thus, prospective surveillance is helpful for earlier institution of anti-viral treatment.