Betaherpesvirus Complications and Management During Hematopoietic Stem Cell Transplantation

Abstract

Two of the four betaherpesviruses, Cytomegalovirus (CMV) and human herpesvirus 6B (HHV-6B), play an important role in opportunistic infections in hematopoietic stem cell transplant (HSCT) recipients. These viruses are ubiquitous in humans and can latently infect mononuclear lymphocytes, complicating the diagnosis of the diseases they cause. Although the detection of viral DNA in a patient's peripheral blood by real-time PCR is widely used for monitoring viral infection, it is insufficient for the diagnosis of virus-associated disease. Theoretically, end-organ disease should be confirmed by detecting either viral antigen or significant amounts of viral DNA in a tissue sample obtained from the involved organ; however, this is often difficult to perform in clinical practice. The frequency of CMV-associated diseases has decreased gradually as a result of the introduction of preemptive or prophylactic treatments; however, CMV and HHV-6B infections remain a major problem in HSCT recipients. Measurement of viral DNA load in peripheral blood or plasma using real-time PCR is commonly used for monitoring these infections. Additionally, recent data suggest that an assessment of host immune response, particularly cytotoxic T-cell response, may be a reliable tool for predicting these viral infections. The antiviral drugs ganciclovir and foscarnet are used as first-line treatments; however, it is well known that these drugs have side effects, such as bone marrow suppression and nephrotoxicity. Further research is required to develop less-toxic antiviral drugs.

Comprehensive Prognostication in Critically Ill Pediatric Hematopoietic Cell Transplant Patients: Results from Merging the Center for International Blood and Marrow Transplant Research (CIBMTR) and Virtual Pediatric Systems (VPS) Registries

“…Although the use of serotherapy and UCB allografts has been associated with increased risk of CMV reactivation [41], neither of these risk factors was associated with PICU mortality in this cohort, again suggesting that although many patients with these risk factors were quite sick, many patients without these risk factors were comparably critically ill for other reasons. Future investigations aimed at minimizing the risk of CMV reactivation, improving early CMV detection in end organs such as the lungs and intestine, and reducing the toxicity of anti-CMV therapies may improve outcomes for this subset of patients [42].…”

Humanization of Murine Neutralizing Antibodies against Human Herpesvirus 6B

“…Reactivation of the betaherpesviruses HHV-6B and human cytomegalovirus (HCMV), along with their complications, has been reported as a major problem in allo-HSCT (12,21). Prophylactic treatments for HCMV have gradually decreased the frequency of HCMV-associated diseases.…”

Hematopoietic stem cells and betaherpesvirus latency

“…Of those that do, even well-matched transplant material of sufficient cells with good function can lead to rejection as a result of graft vs host disease and/or suppressed cell engraftment or immune function due to infectious disease complications. Human betaherpesviruses play a significant role in the success, or lack thereof, of hematopoietic stem cell transplant ( Ljungman, 2010 ; Yoshikawa, 2018 ).…”