Optimizing the treatment of cytomegalovirus infection in allo-HSCT recipients

ABSTRACT

Introduction

Cytomegalovirus (CMV) infection continues to negatively impact the prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT), even with active monitoring and preemptive strategies. Recent progress in pharmacology, immunotherapy, and vaccines has improved the strategy of CMV management.

Areas covered

We summarized recent advances in managing CMV infection post allo-HSCT, including diagnosis, prophylaxis, and treatment. In this review, we mainly focused on approaches that have optimized or might optimize the management of CMV infection after allo-HSCT.

Expert opinion

In our opinion, optimized management covers aspects including the serial monitoring of CMV-DNA and CMI, an accurate diagnosis, effective prophylaxis, and a rational preemptive therapy integrating antiviral drugs and cell therapies. Strategies based on the understanding of CMV pathogenesis and CMV-related immune reconstitution after allo-HSCT will be a direction in future studies.

KEYWORDS:

• Allogeneic hematopoietic stem cell transplantation (allo-HSCT)
• CMV cellular immunity (CMI)
• CMV-specific cytotoxic T-cell (CMV-CTL)
• cytomegalovirus (CMV)
• preemptive therapy (PET)
• prophylaxis
• refractory/resistant CMV (R/R CMV)

Article highlights

• CMV infection is a common complication after allo-HSCT that negatively impacts transplant outcomes. The mortality of CMV disease could be up to 20-70%.

• Nucleic acid-based diagnosis using PCR methods provides a more sensitive and faster diagnosis of CMV infection and could guide early interventions.

• The advent of novel drugs with better safety profiles (such as letermovir) has resuscitated the strategy of general prophylaxis. Prophylaxis with strategies to promote immune reconstitution, such as vaccines and adoptive T-cell infusions, is promising.

• New drugs (such as maribavir) and immune-based therapy (such as CMV-CTL infusions) have improved the prognosis of R/R CMV infection.

• Strategies based on the understanding of CMV pathogenesis and CMV-related immune reconstitution after allo-HSCT will be a direction in future studies.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported (in part) by the National Natural Science Foundation of China (grant no. 8227010768) and the National Key Research and Development Program of China (2021YFC2500300).