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

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.

The impact of alternative donor types on viral infections in pediatric hematopoietic stem cell transplantation

“…They found the incidence of infection‐related mortality was higher after haplo‐HSCT than after HLA‐identical sibling donor HSCT (21.2% vs 13.4%, P = .002). Rustia et al found in their study similarly that the overall survival for patients with viremia and viral disease was significantly lower compared with those without viremia (58% vs 74.2%, P = .03) and viral disease (48.2% vs 71.2%, P = .024). In our study, overall survival was comparable among MUD1/MUD2 and haplo‐HSCT patients, whereas overall survival was superior for patients with MRD‐HSCT ( P < .0001).…”

“…They reported CMV (16%), ADV (15%), and EBV (11%) frequently during period of CD4 T‐cell lymphopenia and found that ADV and EBV reactivations had additional associations with the use of HLA‐mismatched grafts. Rustia et al's study was the third largest study of 140 pediatric patients with 40.7% MRD and 49.3% MUD. They found similar incidence results for CMV (21.4%), ADV (11.4%), and EBV (10%) like Hiwarkar et al.…”

Epidemiology, utilisation of healthcare resources and outcome of invasive fungal diseases following paediatric allogeneic haematopoietic stem cell transplantation

“…Bacterial, viral and fungal infections are frequently observed in children and adolescents post‐transplant . Invasive fungal disease (IFD) is a life‐threatening condition.…”

“…[3][4][5] Bacterial, viral and fungal infections are frequently observed in children and adolescents post-transplant. [6][7][8] Invasive fungal disease (IFD) is a life-threatening condition. Early detection is crucial, but still difficult despite recent progress in the diagnosis of IFDs in immunocompromised hosts.…”

Co-Infections by Double-Stranded DNA Viruses after Ex Vivo T Cell–Depleted, CD34+ Selected Hematopoietic Cell Transplantation

“…Our data provides the benchmark to assess the impact of novel management strategies for dsDNA viruses on health care utilization. A previous study in pediatric HCT has shown that pre-emptive screening and treatment for viruses is more cost-effective than treating viral disease when routine monitoring is not implemented 26 . In recent years, use of donor-derived or third-party viral-specific cytotoxic T lymphocytes have proven effective and safe treatment for viral infections.…”