Biology Reference
In-Depth Information
ch
19
Proteomics in graft-versus-
host disease and graft-
versus-leukemia
Sophie Paczesny
University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA
449
Definition of biomarkers and pending issues for post-
hematopoietic stem cell transplantation clinicians
A biomarker, typically a protein, is defined as a characteristic that can be
objectively measured and evaluated as an indicator of a normal biologic
process, pathogenic process, or pharmacologic response to a therapeutic
intervention
[1]
.
The need for biomarkers post-hematopoietic stem cell transplantation
(HSCT) is due to the limitations of current predictors. Known risk factors
pre-HSCT are related to genetic factors, including HLA disparities between
donor and recipient, age, unrelated transplant, conditioning regimen
intensity, malignant disease status, and donor graft content. A diagnosis of
acute graft-versus-host disease (aGVHD) post-HSCT relies entirely on clini-
cal signs in one of three major target organs, skin, liver, and/or gastroin-
testinal (GI) tract
[2]
, and can be confirmed by biopsies of these organs in
these fragile patients. In addition, histologic severity on biopsy has not been
consistently correlated with clinical outcome
[2]
, and there are no validated
blood tests currently available.
Types of biomarkers
Various types of biomarkers have been identified. Diagnostic biomark-
ers identify the presence of a disease (e.g., aGVHD). Further, surrogates
identify disease in a target organ compared to other complications that
present with the same symptoms in the target organ (e.g., GI GVHD ver-
sus infectious enteritis). Other examples of surrogate markers post-HSCT
are biomarkers that differentiate GVHD from graft-versus-leukemia (GVL)
and vice versa. An ideal diagnostic marker should fulfill several criteria:
(1) high specificity for a given disease (i.e., few false positives); (2) high
sensitivity (i.e., few false negatives); (3) ease of use; (4) standardization;
and (5) clarity and readability of the results. All of these factors will affect
biomarker performance in the clinical setting. Prognostic biomarkers
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