Clinical Study on Monitoring Cytomegalovirus (HCMV) Reactivation After Allogeneic Hematopoietic Stem Cell Transplantation Using High-Performance miRNA Quantification Technology (PSTM-qPCR)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for hematologic malignancies and non-malignant disorders. However, post-transplant immune suppression and delayed immune reconstitution make patients highly susceptible to opportunistic infections, among which human cytomegalovirus (HCMV) infection and reactivation are the most frequent and clinically significant. HCMV reactivation has been associated with increased non-relapse mortality, graft-versus-host disease (GVHD), marrow suppression, and organ-specific disease, significantly affecting patient outcomes.

Current standard monitoring relies on quantitative polymerase chain reaction (qPCR)-based HCMV DNA testing in peripheral blood. While this method has improved patient management, limitations remain. HCMV DNA testing may lack sufficient sensitivity to detect early viral reactivation, leading to missed opportunities for timely pre-emptive therapy. Increasing evidence suggests that HCMV-encoded microRNAs (miRNAs), which play critical roles in viral latency, replication, and immune evasion, may serve as novel biomarkers for earlier detection of HCMV activity.

This prospective, multicenter, observational cohort study will evaluate the diagnostic and predictive performance of HCMV-miRNAs using a novel high-performance detection platform, PSTM-qPCR, developed in collaboration with the National Institute of Diagnostics and Vaccine Development in Infectious Diseases at Xiamen University. PSTM-qPCR offers markedly improved sensitivity and specificity compared with conventional qPCR, with the ability to distinguish single-base differences and detect viral activity earlier.

Approximately 300 allo-HSCT recipients and their donors will be enrolled across seven transplant centers in China. Blood samples will be collected at baseline (pre-transplant) and serially post-transplant (weekly during the first 3 months, monthly through 6 months, and as clinically indicated up to 12 months). Both HCMV-miRNA and HCMV-DNA will be measured. Primary outcome measures include the diagnostic performance of HCMV-miRNA compared with HCMV-DNA for early detection of HCMV infection. Secondary outcomes include rates of HCMV infection and reactivation, HCMV-related mortality and organ disease, GVHD incidence, and overall survival.

The study aims to validate HCMV-miRNA as a reliable early biomarker for HCMV infection in allo-HSCT recipients. By establishing a sensitive and clinically applicable monitoring strategy, this research seeks to improve infection control, guide individualized antiviral therapy, and ultimately enhance survival and quality of life in transplant patients.