The Association Between Gene Expression Profiling Scores and Malignancy in Adult Heart Transplant Recipients

Area of Science:

• Immunology
• Oncology
• Transplantation Medicine

Background:

• Malignancy is a significant concern after heart transplantation (HTx), occurring in 15.3% of patients.
• Immunosuppressive therapy increases cancer risk by impairing immune surveillance against oncogenic viruses.
• Gene expression profiling (GEP; AlloMap) assesses immune quiescence to identify rejection risk.

Purpose of the Study:

• To investigate the association between AlloMap scores and long-term cancer risk post-heart transplantation.
• To determine if GEP reflects immune activity relevant to oncologic outcomes.

Main Methods:

• Retrospective cohort study of 104 adult HTx recipients with AlloMap surveillance >365 days post-transplant.
• Exclusion criteria included pre-transplant malignancy, CMV viremia, or cardiac allograft vasculopathy.
• AlloMap scores modeled as time-varying cumulative means; adjusted for demographics, CMV status, rejection history, and immunosuppression.

Main Results:

• 29% of recipients developed invasive malignancy at a median of 35 months post-transplant.
• Higher cumulative mean AlloMap scores were associated with a lower risk of post-transplant malignancy (HR 0.95 per 5-unit increase).
• Time-varying LOCF or patient-level mean AlloMap scores were not significantly associated with malignancy risk.

Conclusions:

• Longitudinal cumulative AlloMap monitoring, not short-term measures, correlates with post-transplant malignancy risk.
• Sustained low immune activity (low cumulative AlloMap scores) may indicate increased oncologic risk.
• Further validation in larger studies is warranted for immune profiling in malignancy risk stratification.