An update on the treatment of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation

Abstract

Human Cytomegalovirus (CMV) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Frequency of CMV infection and disease after allo-HSCT depend on several factors including virus-host interactions, recipient-donor CMV serology, donor type (HLA-identical vs. haplo-identical donors)and intensity of conditioning regimens. Moreover, monitoring strategies, cutoff values of viremia to guide prophylactic, preemptive, and treatment interventions remain to be determined. Broader knowledge in CMV biology and its relationship with the host immune-system is greatly contributing to develop novel therapeutic approaches including the application of novel antiviral drugs, with improved toxicity profiles currently under investigation in randomized phase II and III trials, and cell therapy approaches. Significant evidence of the clinical efficacy of adoptive T-cell therapy (ATCT) from CMV-seropositive donors is also emerging. Alternative methods allow ATCT also in allo-HSCT recipients of seronegative donors and cord blood grafts. Vaccine-immunotherapy has the difficult task to reduce the incidence of CMV reactivation/infection in immunocompromised allo-HSCT patients and reach CMV immune control. In this manuscript, we update a previous review by also including recent developments in the virology lab and their possible association with treatment strategies at bedside.

Cytomegalovirus preventive strategies in lupus nephritis and renal vasculitis treated with immunosuppressants

“…Prospective multi-centre studies are needed to evaluate the relative clinical merits, safety and cost-effectiveness of respective CMV preventive strategies such as antiviral prophylaxis or surveillance and pre-emptive therapy. Recently, CMV-specific T-cell immune monitoring has been used for CMV risk stratification in both solid organ transplantation and allogenic hematopoietic stem-cell transplantation, 4,5 but its clinical utility has yet to be evaluated in autoimmune disease cohorts and is pending substantive interventional studies. 6 While these approaches seek to lower the risk of early CMV infections during a period of intense immunosuppression, vigilance should be maintained throughout the entire disease and treatment course, as CMV infections may reactivate anytime, as illustrated by Sebastiani et al.…”

Letermovir Prophylaxis for Cytomegalovirus Infection in Allogeneic Stem Cell Transplantation: A Real-World Experience

“…Twenty patients discontinued the trial in the first 100 days, the majority (13 patients) because of death. CSCI has been associated with increased NRM in transplant patients (2)(3)(4)(5)(6). Up until the introduction of LET, no antiviral prophylaxis had proven capable of preventing CSCI in seropositive patients.…”

“…CSCI has been associated with increased NRM in transplant patients ( 2 – 6 ). Up until the introduction of LET, no antiviral prophylaxis had proven capable of preventing CSCI in seropositive patients.…”

“…Clinically significant cytomegalovirus (CMV) infection (CSCI), defined as CMV disease or CMV viremia reactivation after allogeneic stem-cell transplantation (allo-SCT), is often a serious complication given the delayed immune recovery of the host (1)(2)(3). Post-transplant CSCI varies from 30% to 70% and has been associated with higher non-relapse mortality (NRM) (4)(5)(6)(7)(8)(9)(10).…”

T-cell receptor repertoire of cytomegalovirus-specific cytotoxic T-cells after allogeneic stem cell transplantation

“…Human leukocyte antigen (HLA)-specificity adds a further layer of complication to this problem. There have been recent attempts to use T-cell therapy to treat CMV and other viruses [29][30][31][32][33][34][35] . However, as TCRs are restricted by HLA-specificity, when planning to perform T-cell therapy with a third-party donor (TPD) rather than a stem cell donor, it is necessary to have a good understanding of the TCR repertoire specific to that HLA type.…”