Personalized treatment in heart transplantation

Abstract

Purpose of review: We are entering the era of personalized medicine, in which pharmacogenomics and biomarker-based assays can be used to tailor diagnostic tests and drug therapies to individual patients. This new approach to patient-specific care offers the potential to maximize the efficacy of available medical treatments while reducing the incidence of adverse side effects. Here, we present approaches to personalize the care of heart transplant recipients.

Recent findings: Four strategies for personalized posttransplant care are described, including use of pharmacogenomic data to individualize the use of immunosuppressive drugs, immune monitoring to prevent acute rejection while reducing the long-term consequences of over immunosuppression, noninvasive surveillance for acute rejection, and targeted prophylaxis against opportunistic infections.

Summary: The long-term survival of heart transplant recipients is limited by side effects of immunosuppressive drugs, including infectious complications, renal dysfunction, and malignancy. We discuss strategies to maximize the benefits of immunosuppressive and prophylactic therapies while minimizing their long-term toxicities.

Figure 1. Lower anellovirus load in heart transplant recipients with acute rejection

Time dependence of anellovirus load in the subgroup of patients who experience a moderate-severe acute cellular rejection event (biopsy grade≥2R/3A, red data) and in the subgroup of patients with a rejection-free post-transplant course (biopsy grades<2R/3A, blue data). The inset shows the inverse relationship between the level of immunosuppression and the incidence of rejection and infection. Source: De Vlaminck I, et al. Temporal Response of the Human Virome to Immunosuppression and Antiviral Therapy, Cell, 2013 November 21; 155(5) 1178–1187. *Figure 5A from Cell paper*

Figure 2. Performance of donor-derived cell-free DNA as a marker for heart transplant rejection

Box plots of the fraction of donor-derived cell-free DNA for stable heart transplant recipients (biopsy grade 0), recipients diagnosed with mild rejection (1R/1A ≤ grade < 2R/3A), and recipients diagnosed with moderate-to-severe rejection (grade ≥2R/3A or AMR) Source: De Vlaminck, I, et al. Circulating Cell-Free DNA Enables Noninvasive Diagnosis of Heart Transplant Rejection, Science Translational Medicine, 2014 June 18; 6(241) 241ra77. *Figure 5A from Science Translational Medicine paper*