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transplant recipients. A sentinel signature has been characterized raising the possi-
bility of application of blood leukocyte expression signatures for assessment of
immune status and early detection of disease.
According to the NIH consensus development project on criteria for clinical tri-
als in chronic GVHD, the following applications of biomarkers could be useful:
- Predicting response to therapy.
- Measuring disease activity and distinguishing irreversible damage from contin-
ued disease activity. - Predicting the risk of developing chronic GVHD.
- Diagnosing chronic GVHD.
- Predicting the prognosis of chronic GVHD.
- Evaluating the balance between GVHD and graft-versus-leukemia effects
(graft-versus- leukemia or GVT) - Serving as a surrogate end point for therapeutic response.
With the advancement of many high-throughput ‘omics techniques such as
genomics, proteomics, and metabolomics, efforts have been made to understand
potential mechanisms of specifi c graft injuries and develop novel biomarkers for
acute as well as chronic rejection (Sarwal 2009 ). Microarrays are being increasingly
used to identify specifi c patterns of gene expression that predict and characterize
acute and chronic rejection, and to improve the understanding of the mechanisms
underlying organ allograft dysfunction. It is feasible to develop minimally invasive,
rapid tests for prognosis and diagnosis in personalized management of transplanta-
tion patients.
Rashes are very common in patients after bone marrow transplants. They may
signal the onset of acute GVHD. But until now, a skin biopsy was the only reliable
way for doctors to determine whether the rash is caused by antibiotics commonly
used to treat bone marrow transplant patients, or is instead GVHD of the skin, where
the disease appears in about half of cases. Quantitative proteomic studies have
shown that elafi n is overexpressed in GVHD skin biopsies and plasma concentra-
tions of elafi n are signifi cantly higher at the onset of skin GVHD (Paczesny et al.
2010 ). These are correlated with the eventual maximum grade of GVHD, and are
associated with a greater risk of death relative to other known risk factors. Therefore,
elafi n has signifi cant diagnostic and prognostic value as a biomarker of skin
GVHD. The test, which is available to clinicians, can determine the risk a patient
may have for further complications, and thus physicians will be able to adjust ther-
apy to the degree of risk, rather than treating every patient in exactly the same way.
A study compared 12 biomarkers in plasma obtained a median of 16 days after
therapy initiation from patients with a complete response by day 28 after therapy
initiation and in plasma obtained from patients with progressive GVHD during ther-
apy (Vander Lugt et al. 2013 ). The lead biomarker, suppression of tumorigenicity 2
(ST2), had the most signifi cant association with resistance to GVHD therapy and
subsequent death without relapse. As compared with patients with low ST2 values at
therapy initiation, patients with high ST2 values were 2.3 times as likely to have
treatment-resistant GVHD and 3.7 times as likely to die within 6 m after therapy.
17 Personalized Approaches to Immune Disorders