Dataset Information

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 cell-mediated 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.

SUBMITTER: Jakharia N

PROVIDER: S-EPMC8294301 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). The goals of this study were identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with CMV disease, acute GVHD and overall survival. METHODS: The diagnosis of active CMV infection after allogeneic HSCT was detected by antigenemia (AGM) and/or nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment. RESULTS: Sixty-three allogeneic HSCT recipients were prospectively evaluated; 49/63 (78%) patients were infected with CMV genotypes - gB1 19/49 (39%), gB2 17/49 (35%), gB3 3/49 (6%), gB4 7/49 (14%) - and 3 (6%) had mixed CMV genotypes (gB1 + gB3, gB1 + gB4 and gB2 + gB4). Characterized by gastrointestinal disease, CMV disease occurred in 3/49 (6.1%) patients, who had CMV gB3 genotype. These gB3 genotype patients presented an increasing AGM number, mean 125 (± 250) (P = 0.70), and qPCR copies/ml, mean 37938 (SD ± 50542) (P = 0.03), during antiviral treatment, when compared with other CMV genotypes. According to CMV genotypes, stratified overall survival was 55% for gB1, 43% for gB2; 0% for gB3 and 57% for gB4 (P = 0.03). CONCLUSIONS: One of the restrictions of the presented study was the low number of CMV gB sub-cohorts). However, we demonstrated that the frequency of active CMV infection in this HSCT population was high, and the most prevalent genotype in these patients with active CMV infection was gB1 and gB2 genotype (74%). In Brazil, HSCT recipients seem to carry mainly gB1 and gB2 CMV genotype.