Cytomegalovirus in Haematological Tumours

Abstract

The exquisite coupling between herpesvirus and human beings is the result of millions of years of relationship, coexistence, adaptation, and divergence. It is probably based on the ability to generate a latency that keeps viral activity at a very low level, thereby apparently minimising harm to its host. However, this evolutionary success disappears in immunosuppressed patients, especially in haematological patients. The relevance of infection and reactivation in haematological patients has been a matter of interest, although one fundamentally focused on reactivation in the post-allogeneic stem cell transplant (SCT) patient cohort. Newer transplant modalities have been progressively introduced in clinical settings, with successively more drugs being used to manipulate graft composition and functionality. In addition, new antiviral drugs are available to treat CMV infection. We review the immunological architecture that is key to a favourable outcome in this subset of patients. Less is known about the effects of herpesvirus in terms of mortality or disease progression in patients with other malignant haematological diseases who are treated with immuno-chemotherapy or new molecules, or in patients who receive autologous SCT. The absence of serious consequences in these groups has probably limited the motivation to deepen our knowledge of this aspect. However, the introduction of new therapeutic agents for haematological malignancies has led to a better understanding of how natural killer (NK) cells, CD4+ and CD8+ T lymphocytes, and B lymphocytes interact, and of the role of CMV infection in the context of recently introduced drugs such as Bruton tyrosine kinase (BTK) inhibitors, phosphoinosytol-3-kinase inhibitors, anti-BCL2 drugs, and even CAR-T cells. We analyse the immunological basis and recommendations regarding these scenarios.

Improving the safety of CAR‐T‐cell therapy: The risk and prevention of viral infection for patients with relapsed or refractory B‐cell lymphoma undergoing CAR‐T‐cell therapy

“…One hallmark of CMV infection is the persistence of substantial populations of CMV‐specific memory CD8 + T cells. Emerging data indicate that this memory inflation might be linked to compromised immunity, particularly in the elderly 81,82 . As CMV infection rates rise among CAR‐T recipients, understanding the mechanisms linking CMV pathology with CAR‐T cells will be pivotal in future investigations.…”

Current management of CMV infection in cancer patients (solid tumors). Epidemiology and therapeutic strategies

“…For reasons of extension of this manuscript, this section will be summarized in Figure 1 with additional comments. The figure shows how certain families of drugs or therapeutic strategies favour and increase the risk of CMV reactivation or infection in certain settings of oncohematological disease, and how others do not increase this risk or their influence is less or even neutral [ 7 ].…”

“…However, the introduction of new therapeutic agents for solid and haematological malignancies has led to a better understanding of how natural killer (NK) cells, CD4+ and CD8+ T lymphocytes, and B lymphocytes interact, and of the role of CMV infection in the context of recently introduced drugs such as modern immunochemotherapies, immune check-point inhibitors such as programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-1L) inhibitors and cytotoxic T-lymphocyte antigen 4 (CTLA4) inhibitors, Bruton tyrosine kinase (BTK) inhibitors, phosphoinosytol-3-kinase (Pl3K) inhibitors, Janus-kinase (JK) inhibitors, proteasome inhibitors, anti-CD52 blocking agents, purine analogues, anti-BCL2 drugs, and even CAR-T cells therapy [ 7 ].…”

Overlapping Infection by Strongyloides spp. and Cytomegalovirus in the Immunocompromised Host: A Comprehensive Review of the Literature

“…Transmission occurs through organ transplantation of an infected organ or contact with infected bodily secretions [ 6 ]. The spectrum of its clinical manifestation is wide: primary infection often runs asymptomatic or paucisymptomatic in an immunocompetent host [ 7 ]. When symptomatic, the most common presentation is a mononucleosis-like syndrome (i.e., fever, asthenia, rash, lymphadenopathy) and single-organ involvement is unusual.…”