Risk Factors and Utility of a Risk-Based Algorithm for Monitoring Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections in Pediatric Recipients after Allogeneic Hematopoietic Cell Transplantation

• Type of Material: Article
• Authors: Evelyn Rustia, Cornell University; Leah Violago, New York Presbyterian Morgan Stanley Children's Hospital; Zhezhen Jin, Columbia University; Marc D. Foca, Cornell University; Justine M. Kahn, Cornell University; Staci Arnold, Emory University; Jean Sosna, Cornell University; Monica Bhatia, Cornell University; Andrew L. Kung, Cornell University; Diane George, Cornell University; James H. Garvin, Cornell University; Prakash Satwani, Cornell University
• Language: English
• Date: 2016-09-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 American Society for Blood and Marrow Transplantation.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbmt.2016.05.014
• Title of Journal or Parent Work: Biology of Blood and Marrow Transplantation
• ISSN: 1083-8791
• Volume: 22
• Issue: 9
• Start Page: 1646
• End Page: 1653
• Keywords: DISEASES WORKING PARTY; CYTOTOXIC T-LYMPHOCYTES; Pediatrics; THERAPY; Life Sciences & Biomedicine; MARROW-TRANSPLANTATION; EUROPEAN-GROUP; Viral infections; Bone marrow transplantation; CHILDREN; Hematology; VIRAL-INFECTIONS; CMV INFECTIONS; Immunology; VERSUS-HOST-DISEASE; Transplantation; Science & Technology; PROPHYLAXIS
• Research Categories: Biology, Virology; Health Sciences, Public Health

Abstract

Infectious complications, particularly viral infections, remain a significant cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (alloHCT). Only a handful of studies in children have analyzed the risks for and impact of viremia on alloHCT-related outcomes. We conducted a retrospective study of 140 pediatric patients undergoing alloHCT to investigate the incidence of and risk factors for cytomegalovirus (CMV), adenovirus (ADV), and Epstein-Barr virus (EBV) viremia and viral disease after alloHCT. Furthermore, we assessed the impact of viremia on days of hospitalization and develop an algorithm for routine monitoring of viremia. Patients were monitored before alloHCT and then weekly for 180 days after alloHCT. Patients were considered to have viremia if CMV were > 600 copies/mL, EBV were > 1000 copies/mL, or ADV were > 1000 copies/mL on 2 consecutive PCRs. The overall incidences of viremia and viral disease in all patients from day 0 to +180 after alloHCT were 41.4% (n = 58) and 17% (n = 24), respectively. The overall survival for patients with viremia and viral disease was significantly lower compared with those without viremia (58% versus 74.2%, P =.03) and viral disease (48.2% versus 71.2%, P =.024). We identified that pretransplantation CMV risk status, pre-alloHCT viremia, and use of alemtuzumab were associated with the risk of post-alloHCT viremia. The average hospitalization days in patients with CMV risk (P =.011), viremia (P =.024), and viral disease (P =.002) were significantly higher. The algorithm developed from our data can potentially reduce viral PCR testing by 50% and is being studied prospectively at our center. Improved preventative treatment strategies for children at risk of viremia after alloHCT are needed.