CMV Infection in Hematopoietic Stem Cell Transplantation: Prevention and Treatment Strategies

Abstract

Purpose of Review Cytomegalovirus (CMV) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (Allo-HSCT). New strategies and methods for prevention and management of CMV infection are urgently needed. We aim to review the new developments in diagnostics, prevention, and management strategies of CMV infection in Allo-HSCT recipients. Recent Findings The approval of the novel anti-CMV drug letermovir in 2017 has led to an increase in the use of antiviral prophylaxis as a preferred approach for prevention in many centers. Real-world studies have shown efficacy similar to the clinical trial. CMV-specific T cellmediated immunity assays identify patients with immune reconstitution and predict disease progression. Phase 2 trials of maribavir have shown its efficacy as preemptive therapy and treatment of resistant and refractory CMV infections. Adoptive T cell therapy is an emerging option for treatment of refractory and resistant CMV. Of the different CMV vaccine trials, PepVax has shown promising results in a phase 1 trial.Summary CMV cell-mediated immunity assays have potential to be used as an adjunctive test to develop individualized management plan by identifying the patients who develop immune reconstitution; however, further prospective interventional studies are needed. Maribavir and adoptive T cell therapy are promising new therapies for treatment of CMV infections. CMV vaccine trials for prevention are also under way.

Antivirales (a excepción del virus de la inmunodeficiencia humana y la hepatitis)

“…Sin embargo, el bloqueo de la reactivación viral a partir del estado de latencia, si no se logra la erradicación total, basta en ocasiones para prevenir la aparición de signos clínicos. Esta estrategia se apoya en el uso de la quimioterapia antiviral convencional, como lo ha demostrado la prevención de la enfermedad por CMV por los antivirales en los trasplantados de órganos [14] , [15] .…”

“…Esta enzima interviene en la fosforilación de muchas proteínas implicadas en la replicación y el ensamblaje de las partículas virales, así como en la modulación del funcionamiento celular durante la infección viral. También interviene en la fosforilación del GCV como se ha indicado previamente, por lo que se comprende que el maribavir sea un antagonista del GCV [2] , [15] . El desarrollo de este fármaco se ha frenado un poco por los resultados decepcionantes de ensayos de fase III, pero actualmente parece ser útil contra las cepas de CMV resistentes a los antiherpéticos clásicos.…”

“…El letermovir es un inhibidor específico de la terminasa del CMV, un heterodímero codificado por los genes muy conservados UL56 y UL89, y causa pocos efectos secundarios. Se utiliza en ensayos terapéuticos y parece estar indicado en la prevención de la infección por CMV en los pacientes en quienes se ha realizado un injerto de células hematopoyéticas [15] , [26] .…”

Viral Nucleases from Herpesviruses and Coronavirus in Recombination and Proofreading: Potential Targets for Antiviral Drug Discovery

“…The number of patients experiencing serious HHV-related problems is increasing as the number of individuals undergoing hematopoietic stem cell transplants (HSCT) or receiving immunosuppressive chemotherapy grows. Among the most problematic HHVs in the transplant setting are the α-herpesviruses (HSV-1/2) and β-herpesviruses (CMV and HHV-6B) [ 34 , 35 , 36 , 37 ].…”

CXCR6+ and NKG2C+ Natural Killer Cells Are Distinct With Unique Phenotypic and Functional Attributes Following Bone Marrow Transplantation

“…A significant complication after transplant is the reactivation of HCMV, a herpesvirus infection that is generally asymptomatic in healthy people. However, HCMV can become a life-threatening complication in immunocompromised patients and a significant cause of morbidity and mortality ( 42 , 43 ). Interestingly, NK cell recognition of an HCMV encoded UL-40 protein-derived peptide/HLA-E complex has recently been shown to elicit the expansion of NKG2C + NK cells ( 44 ), suggesting that pathogen-derived peptides may modulate NK cell activation through HLA/E-NKG2C interactions.…”