Allogeneic hematopoietic stem cell transplant (HSCT) remains the mainstay in treating many hematologic malignancies. T-cell–depleted grafts designed to reduce graft-vs.-host disease (GVHD) may be ...complicated by severe viral infections that increase morbidity and mortality. Despite the use of antiviral pharmacologic therapy, challenges in controlling viral infections include drug resistance and/or side-effect intolerability. Virus-specific T-cell (VST) therapy is a promising targeted therapy for treating severe or drug-refractory viral infections after HSCT. An integrative review was conducted to inform advanced practitioners of the adverse effects associated with VST. A total of 836 articles were identified using PubMed, Scopus, and CINAHL databases, with 7 included in this review. Studies reviewed indicate that the adverse effects associated with VST therapy are limited and generally treatable. These studies reported low rates of adverse events of mild to moderate severity, including acute, recurrent, chronic, and de novo GVHD; cytokine release syndrome; infusion toxicity; and other adverse events. No deaths were attributed to VSTs in these studies.
There are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitisation to antigens is a serious complication that can occur in prenatal ...medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rh-the most important blood groups-cannot be done with SNP typing alone. We aimed to develop a novel method based on whole-genome sequencing to identify RBC and platelet antigens.
This whole-genome sequencing study is a subanalysis of data from patients in the whole-genome sequencing arm of the MedSeq Project randomised controlled trial (NCT01736566) with no measured patient outcomes. We created a database of molecular changes in RBC and platelet antigens and developed an automated antigen-typing algorithm based on whole-genome sequencing (bloodTyper). This algorithm was iteratively improved to address cis-trans haplotype ambiguities and homologous gene alignments. Whole-genome sequencing data from 110 MedSeq participants (30 × depth) were used to initially validate bloodTyper through comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens. bloodTyper was further validated with whole-genome sequencing data from 200 INTERVAL trial participants (15 × depth) with serological comparisons.
We iteratively improved bloodTyper by comparing its typing results with conventional serological and SNP typing in three rounds of testing. The initial whole-genome sequencing typing algorithm was 99·5% concordant across the first 20 MedSeq genomes. Addressing discordances led to development of an improved algorithm that was 99·8% concordant for the remaining 90 MedSeq genomes. Additional modifications led to the final algorithm, which was 99·2% concordant across 200 INTERVAL genomes (or 99·9% after adjustment for the lower depth of coverage).
By enabling more precise antigen-matching of patients with blood donors, antigen typing based on whole-genome sequencing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine.
National Human Genome Research Institute, Doris Duke Charitable Foundation, National Health Service Blood and Transplant, National Institute for Health Research, and Wellcome Trust.
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