BACKGROUND: We report on predictors of adenovirus (ADV) viremia and correlation of ADV viral kinetics with mortality in ex vivo T-cell depleted (TCD) hematopoietic cell transplant (HCT). METHODS: T cell-depleted HCT recipients from January 1, 2012 through September 30, 2018 were prospectively monitored for ADV in the plasma through Day (D) +100 posttransplant or for 16 weeks after the onset of ADV viremia. Adenovirus viremia was defined as ≥2 consecutive viral loads (VLs) ≥1000 copies/mL through D +100. Time-averaged area under the curve (AAUC) or peak ADV VL through 16 weeks after onset of ADV viremia were explored as predictors of mortality in Cox models. RESULTS: Of 586 patients (adult 81.7%), 51 (8.7%) developed ADV viremia by D +100. Age <18 years, recipient cytomegalovirus seropositivity, absolute lymphocyte count <300 cells/µL at D +30, and acute graft-versus-host disease were predictors of ADV viremia in multivariate models. Fifteen (29%) patients with ADV viremia died by D +180; 8 of 15 (53%) died from ADV. Peak ADV VL (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.52-3.33) and increasing AAUC (HR, 2.95; 95% CI, 1.83-4.75) correlated with mortality at D +180. CONCLUSIONS: In TCD HCT, peak ADV VL and ADV AAUC correlated with mortality at D +180. Our data support the potential utility of ADV viral kinetics as endpoints in clinical trials of ADV therapies.
BACKGROUND: We report on predictors of adenovirus (ADV) viremia and correlation of ADV viral kinetics with mortality in ex vivo T-cell depleted (TCD) hematopoietic cell transplant (HCT). METHODS: T cell-depleted HCT recipients from January 1, 2012 through September 30, 2018 were prospectively monitored for ADV in the plasma through Day (D) +100 posttransplant or for 16 weeks after the onset of ADV viremia. Adenovirusviremia was defined as ≥2 consecutive viral loads (VLs) ≥1000 copies/mL through D +100. Time-averaged area under the curve (AAUC) or peak ADV VL through 16 weeks after onset of ADV viremia were explored as predictors of mortality in Cox models. RESULTS: Of 586 patients (adult 81.7%), 51 (8.7%) developed ADV viremia by D +100. Age <18 years, recipient cytomegalovirus seropositivity, absolute lymphocyte count <300 cells/µL at D +30, and acute graft-versus-host disease were predictors of ADV viremia in multivariate models. Fifteen (29%) patients with ADV viremia died by D +180; 8 of 15 (53%) died from ADV. Peak ADV VL (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.52-3.33) and increasing AAUC (HR, 2.95; 95% CI, 1.83-4.75) correlated with mortality at D +180. CONCLUSIONS: In TCD HCT, peak ADV VL and ADV AAUC correlated with mortality at D +180. Our data support the potential utility of ADV viral kinetics as endpoints in clinical trials of ADV therapies.
Authors: Roni Tamari; Betul Oran; Patrick Hilden; Molly Maloy; Piyanuch Kongtim; Esperanza B Papadopoulos; Gabriela Rondon; Ann A Jakubowski; Borje S Andersson; Sean M Devlin; Sairah Ahmed; Uday R Popat; Doris Ponce; Julianne Chen; Craig Sauter; James W Young; Marcos de Lima; Miguel-Angel Perales; Richard J O'Reilly; Sergio A Giralt; Richard E Champlin; Hugo Castro-Malaspina Journal: Biol Blood Marrow Transplant Date: 2018-01-08 Impact factor: 5.742
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Authors: L Öhrmalm; A Lindblom; H Omar; O Norbeck; I Gustafson; I Lewensohn-Fuchs; J-E Johansson; M Brune; P Ljungman; K Broliden Journal: Bone Marrow Transplant Date: 2010-04-19 Impact factor: 5.483
Authors: Evelyn Rustia; Leah Violago; Zhezhen Jin; Marc D Foca; Justine M Kahn; Staci Arnold; Jean Sosna; Monica Bhatia; Andrew L Kung; Diane George; James H Garvin; Prakash Satwani Journal: Biol Blood Marrow Transplant Date: 2016-05-29 Impact factor: 5.742
Authors: Joshua A Hill; Bryan T Mayer; Hu Xie; Wendy M Leisenring; Meei-Li Huang; Terry Stevens-Ayers; Filippo Milano; Colleen Delaney; Keith R Jerome; Danielle M Zerr; Garrett Nichols; Michael Boeckh; Joshua T Schiffer Journal: Clin Infect Dis Date: 2018-01-18 Impact factor: 9.079