Outcomes of Human Adenovirus Infection and Disease in a Retrospective Cohort of Pediatric Hematopoietic Cell Transplant Recipients

被引:25
作者
Fisher, Brian T. [1 ,2 ,5 ,6 ]
Boge, Craig L. K. [1 ,2 ]
Petersen, Hans [8 ]
Seif, Alix E. [3 ,5 ]
Bryan, Matthew [2 ,5 ,6 ]
Hodinka, Richard L. [9 ]
Cardenas, Ana Maria [4 ,7 ]
Purdy, Dale R. [2 ]
Loudon, Brandon [3 ]
Kajon, Adriana E. [8 ]
机构
[1] Childrens Hosp Philadelphia, Div Infect Dis, 2716 South St,Room 10362, Philadelphia, PA 19146 USA
[2] Childrens Hosp Philadelphia, Ctr Pediat Clin Effectiveness, Philadelphia, PA 19104 USA
[3] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA
[4] Childrens Hosp Philadelphia, Infect Dis Diagnost Lab, Philadelphia, PA 19104 USA
[5] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA
[6] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA
[7] Univ Penn, Dept Pathol, Perelman Sch Med, Philadelphia, PA 19104 USA
[8] Lovelace Resp Res Inst, Infect Dis Program, Albuquerque, NM USA
[9] Univ South Carolina, Sch Med Greenville, Dept Biomed Sci, Greenville Hlth Syst, Greenville, SC USA
基金
美国国家卫生研究院;
关键词
adenoviruses; hematopoietic cells; human; pediatrics; transplantation; CIDOFOVIR; RISK; CHILDREN; VIRUS; EPIDEMIOLOGY; DIAGNOSIS; GLOBULIN; DNA;
D O I
10.1093/jpids/piy049
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Background. Human adenoviruses (HAdVs) are associated with significant morbidity and death after hematopoietic cell transplantation (HCT). In this study, we sought to determine the incidence of HAdV infection among pediatric HCT recipients in the polymerase chain reaction (PCR) testing era, identify risk factors for viremia among patients undergoing HAdV surveillance, and assess the effectiveness of preemptive cidofovir. Methods. A single-center retrospective cohort of patients who underwent a transplant within a 10-year period was assembled. The incidence of and outcomes of patients with HAdV infection and disease were determined by PCR results and chart review. A Cox regression model was used for surveilled allogeneic HCT recipients to identify factors associated with viremia. We also used a discrete-time failure model with inverse probability treatment weights to assess the effectiveness of preemptive cidofovir for infection. Results. Among 572 HCT recipients, 76 (13.3%) had >= 1 sample that was HAdV PCR positive (3.5% of autologous HCT recipients and 19.7% of allogeneic HCT recipients). Among 191 allogeneic HCT recipients under surveillance, 58 (30.4%) had HAdV detected from any source, and 50 (26.2%) specifically had viremia. The mortality rate was higher in allogeneic HCT recipients with HAdV infection versus those without infection (25.9% vs 11.3%; P = .01). Factors associated with infection included an age of 6 to 12 years, an absolute lymphocyte count of <200 cells/mu L, recent prednisone exposure, and recent bacteremia. Preemptive cidofovir was not associated with a reduced risk of infection progression (odds ratio, 0.96 [95% confidence interval, 0.30-3.05]). Conclusions. HAdV infection is common and associated with an increased rate of death after allogeneic HCT. Using prediction models that incorporate factors associated with HAdV might help target surveillance. Preemptive cidofovir therapy was not protective in a subset of HAdV-positive patients. Larger observational or randomized investigations are necessary, because the utility of surveillance requires effective preemptive therapies.
引用
收藏
页码:317 / 324
页数:8
相关论文
共 32 条
[1]   High-risk adenovirus-infected pediatric allogeneic hematopoietic progenitor cell transplant recipients and preemptive cidofovir therapy [J].
Anderson, Evan J. ;
Guzman-Cottrill, Judith A. ;
Kletzel, Morris ;
Thormann, Kimberly ;
Sullivan, Christine ;
Zheng, Xiaotian ;
Katz, Ben Z. .
PEDIATRIC TRANSPLANTATION, 2008, 12 (02) :219-227
[2]   Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies [J].
Austin, Peter C. ;
Stuart, Elizabeth A. .
STATISTICS IN MEDICINE, 2015, 34 (28) :3661-3679
[3]   Incidence and outcome of Adenovirus disease in transplant recipients after reduced-intensity conditioning with alemtuzumab [J].
Avivi, I ;
Chakrabarti, S ;
Milligan, DW ;
Waldmann, H ;
Hale, G ;
Osman, H ;
Ward, KN ;
Fegan, CD ;
Yong, K ;
Goldstone, AH ;
Limb, DC ;
MacKinnon, S .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2004, 10 (03) :186-194
[4]   PCR diagnostics and monitoring of adenoviral infections in hematopoietic stem cell transplantation recipients [J].
Bil-Lula, Iwona ;
Ussowicz, Marek ;
Rybka, Blanka ;
Wendycz-Domalewska, Danuta ;
Ryczan, Renata ;
Gorczynska, Ewa ;
Kalwak, Krzysztof ;
Wozniak, Mieczyslaw .
ARCHIVES OF VIROLOGY, 2010, 155 (12) :2007-2015
[5]   Adenovirus infections following allogeneic stem cell transplantation: incidence and outcome in relation to graft manipulation, immunosuppression, and immune recovery [J].
Chakrabarti, S ;
Mautner, V ;
Osman, H ;
Collingham, KE ;
Fegan, CD ;
Klapper, PE ;
Moss, PAH ;
Milligan, DW .
BLOOD, 2002, 100 (05) :1619-1627
[6]   Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group [J].
De Pauw, Ben ;
Walsh, Thomas J. ;
Donnelly, J. Peter ;
Stevens, David A. ;
Edwards, John E. ;
Calandra, Thierry ;
Pappas, Peter G. ;
Maertens, Johan ;
Lortholary, Olivier ;
Kauffman, Carol A. ;
Denning, David W. ;
Patterson, Thomas F. ;
Maschmeyer, Georg ;
Bille, Jacques ;
Dismukes, William E. ;
Herbrecht, Raoul ;
Hope, William W. ;
Kibbler, Christopher C. ;
Kullberg, Bart Jan ;
Marr, Kieren A. ;
Munoz, Patricia ;
Odds, Frank C. ;
Perfect, John R. ;
Restrepo, Angela ;
Ruhnke, Markus ;
Segal, Brahm H. ;
Sobel, Jack D. ;
Sorrell, Tania C. ;
Viscoli, Claudio ;
Wingard, John R. ;
Zaoutis, Theoklis ;
Bennett, John E. .
CLINICAL INFECTIOUS DISEASES, 2008, 46 (12) :1813-1821
[7]   Epidemiology of viral respiratory tract infections in a prospective cohort of infants and toddlers attending daycare [J].
Fairchok, Mary P. ;
Martin, Emily T. ;
Chambers, Susan ;
Kuypers, Jane ;
Behrens, Melinda ;
Braun, LoRanee E. ;
Englund, Janet A. .
JOURNAL OF CLINICAL VIROLOGY, 2010, 49 (01) :16-20
[8]   Adenovirus infection and disease in paediatric haematopoietic stem cell transplant patients: clues for antiviral pre-emptive treatment [J].
Feghoul, L. ;
Chevret, S. ;
Cuinet, A. ;
Dalle, J-H ;
Ouachee, M. ;
Yacouben, K. ;
Fahd, M. ;
Guerin-El Khourouj, V. ;
Roupret-Serzec, J. ;
Sterkers, G. ;
Baruchel, A. ;
Simon, F. ;
LeGoff, J. .
CLINICAL MICROBIOLOGY AND INFECTION, 2015, 21 (07) :701-709
[9]   Deaths attributed to pediatric complex chronic conditions: National trends and implications for supportive care services [J].
Feudtner, C ;
Hays, RM ;
Haynes, G ;
Geyer, JR ;
Neff, JM ;
Koepsell, TD .
PEDIATRICS, 2001, 107 (06) :E99
[10]   INCREASING INCIDENCE OF ADENOVIRUS DISEASE IN BONE-MARROW TRANSPLANT RECIPIENTS [J].
FLOMENBERG, P ;
BABBITT, J ;
DROBYSKI, WR ;
ASH, RC ;
CARRIGAN, DR ;
SEDMAK, GV ;
MCAULIFFE, T ;
CAMITTA, B ;
HOROWITZ, MH ;
BUNIN, N ;
CASPER, JT .
JOURNAL OF INFECTIOUS DISEASES, 1994, 169 (04) :775-781