title: Adenovirus Viremia in Adult CD34(+) Selected Hematopoietic Cell Transplant Recipients: Low Incidence and High Clinical Impact.
abstract: Adenovirus (ADV) infections after hematopoietic cell transplantation (HCT) range in severity from self-limited to fatal. We have previously reported high mortality rates in CD34(+) selected T cell-depleted (TCD) HCT recipients using symptomatic testing and culture methods for ADV detection. We report rates and outcomes of ADV viremia in 215 adult recipients of TCD HCT using the CliniMACS CD34(+) selection system. This was a prospective observational study of adults transplanted from March 21, 2012 through November 30, 2014 at Memorial Sloan-Kettering Cancer Center. TCD was performed using CliniMACS CD34(+) cell selection. Patients were monitored for ADV by whole blood PCR assay from +14 to +100 days post-transplant. ADV viremia was defined as ≥1 PCR above the lower limit of quantitation. ADV disease was defined per European Group for Blood and Marrow Transplantation guidelines. Treatment for ADV was at the clinician's discretion. Competing risk regression analyses were used to identify predictors for ADV viremia and overall survival. The median age was 55 years (range, 22 to 72); 215 patients underwent TCD. All patients received myeloablative conditioning. Eighteen patients (8% of cohort) had ADV viremia at a median onset of 57 days (interquartile range [IQR], 23 to 79) and with a median viral load at first detection of 2.6 log10 copies/mL (IQR, 2.5 to 4.0). The median maximal viral load was 4.5 log10 copies/mL (IQR, 3.5 to 5.9). No significant risk factor was identified for ADV viremia by univariate analysis. Six patients (3% of total cohort, 33% of viremic patients) developed ADV disease (3 colitis, 2 nephritis/cystitis, 1 pneumonitis). ADV viremia preceded onset of ADV disease a median of 11 days from the first positive quantitative PCR (range, +3 to +37) except in 1 patient with nephritis. Overall, 12 of 18 viremic patients (67%) received antiviral treatment (5 cidofovir only, 7 brincidofovir ± cidofovir). All patients with ADV disease were treated, and 6 patients were preemptively treated for ADV. Among the 18 viremic patients, 8 (44%) died during the study period, and, of those, 4 (22%) died of ADV. Early ADV viremia was infrequent (8%) among adult HCT recipients of CD34(+) selected allografts. Among viremic patients, rate of ADV disease was 33% and ADV attributable mortality was 22%. Further studies are needed to assess the impact of preemptive treatment with brincidofovir on improving outcomes of ADV infections in this patient population.
authors: Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York; Weill Cornell Medical College, Cornell University, New York, New York.
authors: Yeon Joo
authors: YJ
authors: Lee
authors: Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Yao-Ting
authors: YT
authors: Huang
authors: Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Seong Jin
authors: SJ
authors: Kim
authors: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Molly
authors: M
authors: Maloy
authors: Weill Cornell Medical College, Cornell University, New York, New York; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Roni
authors: R
authors: Tamari
authors: Weill Cornell Medical College, Cornell University, New York, New York; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Sergio A
authors: SA
authors: Giralt
authors: Weill Cornell Medical College, Cornell University, New York, New York; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Esperanza B
authors: EB
authors: Papadopoulos
authors: Weill Cornell Medical College, Cornell University, New York, New York; Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Ann A
authors: AA
authors: Jakubowski
authors: Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York; Weill Cornell Medical College, Cornell University, New York, New York. Electronic address: papanicg@mskcc.org.
authors: Genovefa A
authors: GA
authors: Papanicolaou
mesh_terms: D000256:Adenoviridae; D000257:Adenoviridae Infections / Q000209:etiology / Q000401:mortality; D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D015331:Cohort Studies; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D014766:Viremia
chemical_list: D018952:Antigens, CD34
keywords: Adenovirus; CD34(+) selected; Hematopoietic cell transplant; T cell depleted