title: Patient, virus, and treatment-related risk factors in pediatric adenovirus infection after stem cell transplantation: results of a routine monitoring program.
abstract: Human adenovirus (HAdV) infection after hematopoietic stem cell transplantation (HSCT) is associated with significant morbidity and mortality in children. The optimal surveillance and treatment strategies are under discussion. Here, we present data from 238 consecutive pediatric allogeneic HSCT recipients who underwent transplantation in a single center who were included in a prospective, weekly HAdV DNAemia monitoring program by quantitative PCR. HAdV loads >1000 copies/mL were detected in 15.5% of all patients. Despite a low mortality directly attributed to HAdV infection (2 patients, 0.84%), blood HAdV loads >10,000 copies/mL (6.7% of all patients) were significant and independent risk factors for poor survival. We searched for patient, virus, and treatment-related risk factors of HAdV DNAemia and disease. Detection of HAdV in blood before day 50 post transplantation was a major independent risk factor for the development of blood HAdV loads >10,000 copies/mL. HAdV typing revealed A31, C1, and C2 as the predominant pathogens among several other HAdV strains with type C species detected in most patients with severe HAdV disease. Stool HAdV loads were prospectively monitored in 111 patients and correlated with but did not significantly precede detection in blood. Treatment with cidofovir led to stable or reduced viral load in 70% of patients with blood HAdV loads >1000 copies/mL. Thus, early occurrence of HAdV-DNA in blood of pediatric HSCT recipients predisposes for development of high viral loads. Control of HAdV infections was attempted by preemptive cidofovir treatment of patients with high blood HAdV loads or with symptomatic organ infections and correlated with low HAdV-attributed mortality.
authors.affiliation: Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Mynarek
authors.affiliation: Department of Virology, Hannover Medical School, Hannover, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Ganzenmueller
authors.affiliation: Institute for Biostatistics, Hannover Medical School, Hannover, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Mueller-Heine
authors.affiliation: Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Mielke
authors.affiliation: Institute for Biostatistics, Hannover Medical School, Hannover, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gonnermann
authors.affiliation: Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Beier
authors.affiliation: Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Sauer
authors.affiliation: Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany; Institute of Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Eiz-Vesper
authors.affiliation: Department of Pharmacy, Hannover Medical School, Hannover, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Kohstall
authors.affiliation: Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Sykora
authors.affiliation: Department of Virology, Hannover Medical School, Hannover, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Heim
authors.affiliation: Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany. Electronic address: maecker.britta@mh-hannover.de.
authors.forename: Britta
authors.initials: B
authors.lastname: Maecker-Kolhoff
mesh_terms: D000257:Adenoviridae Infections / Q000209:etiology* / Q000628:therapy* / Q000821:virology; D002648:Child; D005260:Female; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors
keywords: Human adenovirus; Pediatric transplantation; Stem cell transplantation; Surveillance strategy