560
moderate/severe acute cellular rejection at the time of testing. IMAGE study in 2010
showed the non-inferiority of clinical outcomes of heart transplant recipients managed
with the AlloMap test compared with conventional endomyocardial biopsy. CareDx is
exploring the use of cell-free DNA as a biomarker for rejection in heart transplants.
Prediction of Rejection for Personalizing Anti-rejection Treatment
Surgical techniques have improved survival rates for pediatric organ transplantation
dramatically over the last 25 years. As a result, the challenge has shifted to improv-
ing quality of life. Anti-rejection medications are important because, while they
make transplantation possible, but they also can have adverse side effects that can
themselves become life-threatening, such as infections and cancers. In order to
improve this situation, the NIH awarded a research grant to Children’s Hospital of
Pittsburgh to study genetic factors that could predispose transplant recipients to
rejection. Pre-transplant prediction of which patients are more likely to experience
rejection may be used to tailor anti-rejection medications accordingly. Multiple pro-
cesses that cause rejection in blood cells have been studied and this information will
be linked to the unique “genomic fi ngerprint” of liver transplant candidates, based
on the inheritance of >500,000 mutations or SNPs from parent to child. These muta-
tions can be transmitted from parent to child in certain patterns that indicate if a
transplant candidate is predisposed to rejection, a rejection-free state or tolerance, a
rare occurrence whereby anti-rejection medications no longer are required. Based
on the results of this study, a patient more likely to reject a transplanted organ may
someday receive high doses of anti-rejection medicine initially. Those who are less
likely to reject could have lower doses, or less potent combinations. By applying
individualized anti-rejection strategies before the transplant even occurs, the inves-
tigators hope to reduce rejection rates and drug-induced side effects for pediatric
liver transplant from 50 % to ~20 %.
Personalized Immunosuppressant Therapy in Organ Transplants
Organ transplants are one of the earlier examples of personalized therapy in which
organs are matched to the individuals. In spite of this graft-versus-host disease and
organ reject remain signifi cant problems. Several immunosuppressent therapies are
available now and the responses of individual patients to these vary.
Because of all the drug toxicities, one of the major challenges in treatment fol-
lowing transplant surgery is to determine the proper regimen of immunosuppressant
drugs needed for a patient to prevent rejection of the transplanted organ. Patients
must be given a strong enough dose of the drugs so that their immune systems are
kept in check. At the same time, they cannot receive so high a dose that the drugs
are toxic to the new kidneys. Balancing the need for more with the need for less is
made more diffi cult by the fact that every patient responds differently to the immu-
nosuppressant drugs.
17 Personalized Approaches to Immune Disorders