<p>Epidemiology, Outcome and Risk Factors Analysis of Viral Infections in Children and Adolescents Undergoing Hematopoietic Cell Transplantation: Antiviral Drugs Do Not Prevent Epstein–Barr Virus Reactivation</p>

Abstract

ObjectiveThe analysis of epidemiology, risk factors and outcome of viral infections in children and adolescents after hematopoietic cell transplantation (HCT).MethodsIn this multicenter nationwide study a total of 971 HCT procedures (741 allo-HCT; 230 auto-HCT) over a period of 6 years were analyzed.ResultsDuring this period 801 episodes of viral infections were diagnosed in 442 patients. The incidence of viral infections was 57.9% in allo-HCT and 4.8% in auto-HCT patients. The most frequent infections after allo-HCT were caused by cytomegalovirus (CMV), polyoma BK virus (BKV) and Epstein–Barr virus (EBV). The majority of infections occurred within the first 4 months after allo-HCT and over 80% required pharmacotherapy or symptomatic therapy. The median time of treatment of specific viral infection ranged from 7 (for EBV) to 24 (for CMV) days. The highest mortality was observed in case of CMV infection. The risk factors for viral infections were allo-HCT, acute leukemia, acute and chronic graft versus host disease (a/cGVHD), and matched unrelated donor (MUD)/mismatched unrelated donor (MMUD)-HCT. The risk factor for death from viral infection were CMV-IgG seropositivity in acute lymphoblastic leukemia recipient, and MUD/MMUD-HCT. The incidence of EBV infection requiring pre-emptive treatment with rituximab in allo-HCT children was 19.3%. In 30.8% cases of EBV infection, these episodes were preceded by other viral infection and treated with antivirals, which did not prevent development of EBV-DNA-emia with need of rituximab treatment in 81.5% cases. In 47.7% of these cases, GVHD was a factor enabling development of significant EBV-DNA-emia during antiviral therapy of other infection.ConclusionWe have shown that antiviral drugs do not prevent EBV reactivation in allo-HCT pediatric patients.

Association between Antiviral Prophylaxis and Cytomegalovirus and Epstein–Barr Virus DNAemia in Pediatric Recipients of Allogeneic Hematopoietic Stem Cell Transplant

“…Hann et al [48] also found no reduction in the risk of EBV with the use of acyclovir in a randomized study. Similarly, Paula et al [49], Krzysztof et al [50], and Zutter et al [51] showed no effect of acyclovir on EBV incidence. To our knowledge, no study on famciclovir and EBV has been conducted among pediatric HSCT recipients.…”

Sequential infection of Epstein‐Barr virus and cryptococcal encephalitis after umbilical cord blood transplantation in a child with X‐linked adrenoleukodystrophy

“…Antiviral drugs (ganciclovir or aciclovir) were used in the cases of EBV reactivation, but may not prevent EBV reactivation in the transplant recipient. 9 Rituximab is the first line therapy to remove B lymphocytes infected with EBV. And EBV-specific cytotoxic T lymphocytes as an adoptive T-cell therapy may play a role for immunomodulation in the management of EBV encephalitis.…”

Systemic viral infection in children receiving chemotherapy for acute leukemia

“…In this patient population, algorithms of surveillance, antiviral prophylaxis, and/or preemptive treatment are well established for a number of viruses. [1][2][3] These include routine prophylaxis with acyclovir to suppress herpes simplex virus (HSV) and varicella zoster virus (VZV) reactivation, prophylaxis or preemptive therapy to control cytomegalovirus (CMV) reactivation, and preemptive therapy in patients with adenovirus viremia. 4 In contrast to allogeneic HSCT recipients, data on systemic viral infections in children receiving therapy for acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) are very limited.…”

“…Systemic viral diseases by common viral pathogens are a frequent cause for morbidity and mortality in severely immunocompromised pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In this patient population, algorithms of surveillance, antiviral prophylaxis, and/or preemptive treatment are well established for a number of viruses 1‐3 . These include routine prophylaxis with acyclovir to suppress herpes simplex virus (HSV) and varicella zoster virus (VZV) reactivation, prophylaxis or preemptive therapy to control cytomegalovirus (CMV) reactivation, and preemptive therapy in patients with adenovirus viremia 4 …”