title: Making the genomic leap in HCT: application of second-generation sequencing to clinical advances in hematopoietic cell transplantation.
abstract: Recent developments in second-generation sequencing (SGS) technologies provide an avenue for achieving rapid and accurate high-throughput analysis of human and microbial genomic diversity. SGS technologies have the potential to transform existing medical management of complex and life-threatening medical conditions by enabling clinicians to develop disease-targeted clinical care plans for each patient. In this review, we outline how innovative SGS-based approaches can improve the care of recipients of allogeneic hematopoietic cell transplantation (HCT), a life-saving procedure that carries a 1-year mortality risk of over 30%. We specifically evaluate foreseeable applications of SGS-based technology in facilitating rapid, phase-sensitive human leukocyte antigen (HLA) typing, assessment of non-HLA genomic compatibility, identifying patients at high risk for adverse drug reactions, and post-HCT monitoring for engraftment, minimal residual disease and infection. We conclude that innovative SGS approaches have the capacity to revolutionize the HCT recipient risk assessment process, support non-invasive clinical monitoring and improve patient outcomes, thereby setting the stage for a new era of genomically informed patient-centered medicine.
authors.affiliation: 1] Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA [2] Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Yun R
authors.initials: YR
authors.lastname: Li
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Levine
authors.affiliation: 1] Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA [2] Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA [3] Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: 1] Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA [2] Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA [3] Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA [4] Division of Transplantation, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Keating
mesh_terms: D023281:Genomics / Q000379:methods* / Q000639:trends; D006680:HLA Antigens / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods* / Q000639:trends; D006650:Histocompatibility Testing / Q000379:methods* / Q000639:trends; D006801:Humans; D057170:Translational Research, Biomedical / Q000379:methods / Q000639:trends
chemical_list: D006680:HLA Antigens