letermovir and Postoperative-Complications

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become one of the standard treatment for hematological diseases. Although the clinical outcome has improved significantly during the last decades, the morbidity and mortality after allo-HSCT are still obstacles to cure. Out of major morbidities, opportunistic virus infections such as cytomegalovirus (CMV) infection are important complications, in particular in patients who received human leukocyte antigen-mismatched HSCT. Here, we aim to summarize information about current and future therapeutic options in CMV disease after allo-HSCT.. Recently, not only new drugs but also adoptive T-cell therapy are tested in the setting of clinical trials. CMV prophylaxis using letermovir significantly reduced the incidence of CMV disease in comparison to placebo in a phase III clinical trial. Meanwhile, adoptive T-cell therapies which are fully adapted to good manufacturing practice (GMP) conditions are now available. A recent multicenter study in Germany showed a promising result using Streptamer-isolated T-cell therapy.. With the recent development of CMV-targeted therapy, treatment strategies of CMV infection would be further sophisticated in the near future. VIDEO ABSTRACT: http://links.lww.com/COID/A19.

Topics: Acetates; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Forecasting; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive; Opportunistic Infections; Postoperative Complications; Quinazolines; Transplant Recipients

Human cytomegalovirus (HCMV) represents the major viral complication after hematopoietic stem cell transplantation. HCMV infection may be controlled by the reconstituting immune system and remain subclinical or can lead to severe systemic and/or organ disease (mainly pneumonia and gastroenteritis) when immune reconstitution is delayed or impaired. In order to prevent the occurrence of HCMV disease, a prompt diagnosis of HCMV infection is mandatory. The adoption of pre-emptive therapy strategies guided by virological monitoring dramatically reduced the occurrence of HCMV disease. However, late-onset end-organ disease may occur in some patients with apparent immune reconstitution. In the near future, introduction of immunological monitoring and immunotherapies could markedly improve management of HCMV infection.

Topics: Acetates; Adult; Animals; Antiviral Agents; Asymptomatic Diseases; Benzimidazoles; Clinical Trials as Topic; Cytomegalovirus; Cytomegalovirus Infections; Cytosine; Disease Management; Gastroenteritis; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy; Monitoring, Immunologic; Organophosphonates; Pneumonia; Postoperative Complications; Quinazolines; Ribonucleosides

Letermovir is an antiviral agent indicated for primary prophylaxis of cytomegalovirus (CMV) infection and disease in adult allogeneic hematopoietic stem cell transplant recipients. In this case, UL97 mutation that conferred resistance to ganciclovir was seen in a patient 8 months after renal transplant. We report the off-label use of letermovir with adjunct hyperimmune CMV immunoglobulin in the successful treatment of CMV disease. This report is the first to use this combination for treatment of CMV infection with a high viral load. It contributes to the limited available literature supporting the use of letermovir in the treatment of resistant CMV, where current therapeutic options can be suboptimal due to adverse effects and the risk of cross-resistance.

Topics: Acetates; Antibodies, Viral; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Resistance, Viral; Ganciclovir; Humans; Immunoglobulins, Intravenous; Kidney Transplantation; Male; Middle Aged; Mutation; Postoperative Complications; Quinazolines; Viral Load; Viremia