Control of Cytomegalovirus Viremia after Allogeneic Stem Cell Transplantation: A Review on CMV-Specific T Cell Reconstitution

Abstract

Recipients of allogeneic stem cell transplantation (alloSCT) are at risk for reactivation of endogenous herpesviruses due to profound and prolonged T cell deficiency following conditions such as graft-versus-host disease, immunosuppression, and/or T cell depletion. Reactivation of endogenous cytomegalovirus (CMV) is the most frequently occurring herpesvirus reactivation following alloSCT. Antiviral medication is often used in pre-emptive treatment strategies initiated when increases in CMV viral loads are detected as a result of active reactivation of the virus. Despite pre-emptive antiviral treatment, the incidence of CMV disease in CMV-seropositive alloSCT patients is still 10% at 1 year following alloSCT. This illustrates the necessity for adequate CMV-specific T cell immunity for long-term control of CMV and prevention of CMV disease. In this review, we analyzed the available studies on the influence of donor CMV status on CMV-specific T cell reconstitution and CMV disease. Furthermore, we reviewed the available studies on the safety and efficacy of adoptive transfer of donor CMV-specific T cells for the prevention and treatment of CMV disease following alloSCT, including studies on adoptive transfer of third-party CMV-specific T cells as a possible alternative when donor T cells are not available.

Use of low cell dose for unmanipulated donor lymphocyte for management of cytomegalovirus infection: A single‐center experience

“…[11][12][13] The spectrum of CMV infection is quite broad, from CMV reactivation without any organ involve- Alternatively, techniques for the isolation of virus-specific T-cells have improved in the last two decades. [4][5][6]14 Virus-specific T-cells can be generated by ex vivo expansion of donor peripheral blood mononuclear cells. Traditionally, DLI has been used to boost anti-leukemic/antitumor immunity, but it can also exert antiviral effects.…”

Antigen-Specific TCR Signatures of Cytomegalovirus Infection

“…Such public TCR sequences will find application in various fields. In clinical research, public TCR sequences may be used as indicators to track virus-specific T cell responses in patients after transplantation to identify epitopes that mobilize a protective T cell response against pathogens such as CMV (6). Virus-specific TCR signatures may also be exploited in diagnostics and disease monitoring (36,73,74) to inform about a patient's status regarding past or present infection with multiple pathogens, success of vaccination or T cell transfer, and risk of future infection or reactivation.…”

“…Re-establishment of a functional and durable antiviral T cell repertoire is expected to enable patients to control CMV infection for their lifetime. Transfer of CMV-specific T cells from immunocompetent donors to patients after allogeneic hematopoietic stem cell transplantation has yielded encouraging results over the last three decades (5,6). However, most of these trials were of small to medium scale and without randomized controls.…”

Letermovir and its role in the prevention of cytomegalovirus infection in seropositive patients receiving an allogeneic hematopoietic cell transplant

“…Once the virus reactivates, pre-emptive anti-CMV therapy is initiated to prevent progression to CMV end-organ disease. 1,6 While this approach has decreased the incidence of CMV end-organ disease, the impact on overall morbidity and mortality that is associated with CMV viremia in allo-HCT recipients is still unclear. 2,3,7 The development of a safe and effective agent for prophylaxis, one that would prevent CMV reactivation and disease while avoiding significant toxicities, has been an area of unmet need in CMV management.…”