Genomic screening and complications of hematopoietic stem cell transplantation: has the time come?
The occurrence of toxic complications following hematopoietic stem cell transplantation (HSCT) is highly variable and dependent on a multitude of host, donor, and treatment factors. The increasingly broad indications for HSCT and the need to provide this treatment option to older and/or more debilitated patients emphasizes the importance of refining our methods of predicting and ameliorating these toxicities. Late complications (occurring after day 100) also pose a threat to quality of life after HSCT. Genetic polymorphisms in key molecular pathways in the host are likely to contribute significantly to the observed variability in the development HSCT-associated complications. Hepatic veno-occlusive disease and acute lung injury, two of the most serious organ toxicities that occur, represent useful paradigms for the identification of genetic polymorphisms in enzyme systems that modulate local and systemic responses to oxidant stress during transplant conditioning therapy. Ongoing studies in this area are providing clues to the prevention of adverse clinical outcomes based on the genetic milieu. This review of studies in HSCT that explore genetic risk factors for transplant complications indicates that significant progress is being made in this rapidly evolving area. However, further large-scale clinical and translational studies are needed before genomic screening can be widely used to individualize treatment.
Department of Medicine, Center for Health Services Research, Vanderbilt University Medical Center and TN Valley Health Services VA Medical Center, 1310 24th Avenue South, Nashville, TN 37212, USA. asha.kallianpur@vanderbilt.edu
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D000483:Alleles; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D016678:Genome; D005838:Genotype; D006085:Graft Survival; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006504:Hepatic Veno-Occlusive Disease / Q000235:genetics; D006801:Humans; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008171:Lung Diseases / Q000235:genetics; D008403:Mass Screening; D008727:Methotrexate / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008954:Models, Biological; D008956:Models, Chemical; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000494:pharmacology; D011110:Polymorphism, Genetic; D051437:Renal Insufficiency; D012307:Risk Factors; D013997:Time Factors; D019172:Transplantation Conditioning; D016896:Treatment Outcome
D016877:Oxidants; D007501:Iron; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate