Improving haematopoietic cell transplantation outcomes by selection of an HLA-matched unrelated donor is best practice; however, donor selection by secondary characteristics is controversial. We studied 1271 recipients with haematological malignancies who underwent T-cell-depleted allografts and had complete data on HLA-matching status for six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) and clinical outcome data. Five-year overall survival was 40.6%. HLA mismatching (at HLA-A, -B, -C, -DRB1, -DQB1) relative risk (RR) 1.22, 95% confidence interval (CI) 1.2-1.5, P=0.033 for 1 mismatch and RR 1.46, 95% CI 1.1-1.9, P=0.009 for >1 mismatch) and CMV mismatching (RR 1.37, 95% CI 1.2-1.6, P<0.001) were significantly associated with inferior survival. Donors aged <30 years showed a trend towards better survival. The multivariate model for mortality, combining CMV and HLA-match status, found an RR of 1.36 (95% CI 1.1-1.7, P=0.003) for HLA matched/CMV mismatched, an RR of 1.22 (95% CI 0.99-1.5, P=0.062) for HLA mismatched/CMV matched and an RR of 1.81 (95% CI 1.4-2.3, P=<0.001) for HLA/ CMV mismatched, compared with the HLA/CMV-matched recipients. These data suggest that HLA and CMV matching status should be considered when selecting unrelated donors and that CMV matching may abrogate the effect of an HLA mismatch.
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http://dx.doi.org/10.1038/bmt.2016.352 | DOI Listing |
PLoS One
December 2024
The Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Background: Exposure of critically ill patients to antibiotics lead to intestinal dysbiosis, which often manifests as antibiotic-associated diarrhoea. Faecal microbiota transplantation restores gut microbiota and may lead to faster resolution of diarrhoea.
Methods: Into this prospective, multi-centre, randomized controlled trial we will enrol 36 critically ill patients with antibiotic-associated diarrhoea.
Cytotherapy
November 2024
Scottish National Blood Transfusion Service, Edinburgh, UK; Global Alliance for iPSC Therapies, Jack Copland Centre, Heriot-Watt Research Park, Edinburgh, UK.
Background: Several countries have either developed or are developing national induced pluripotent stem cell (iPSC) banks of cell lines derived from donors with HLA homozygous genotypes (two identical haplotypes) prevalent in their local populations to provide immune matched tissues and cells to support regenerative medicine therapies. This 'haplobank' approach relies on knowledge of the HLA genotypes of the population to identify the most beneficial haplotypes for patient coverage, and ultimately identify donors or cord blood units carrying two copies of the target haplotype.
Aims: A potentially more efficient alternative to a national bank approach is to assess the haplotypes required to provide global patient coverage and to produce a single, global haplobank.
Lancet Rheumatol
December 2024
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Pharming Healthcare, Warren, NJ, USA. Electronic address:
Background: Systemic juvenile idiopathic arthritis-related lung disease (sJIA-LD) is a severe complication in patients with treatment-refractory systemic juvenile idiopathic arthritis (sJIA). The objective of this study was to evaluate the effect of allogeneic haematopoietic stem-cell transplantation (HSCT) in a cohort of children with sJIA-LD.
Methods: This international, retrospective cohort study was performed in nine hospitals across the USA and Europe in children with sJIA-LD who had received allogeneic HSCT.
Transpl Immunol
December 2024
Tissue Typing Centre, Clinical Department for Transfusion Medicine and Transplantation Biology, University Hospital Centre Zagreb, Croatia.
This retrospective study analyses the impact HLA heterozygosity, supertypes, and alleles have on incidence of graft versus host disease (GvHD), relapse, overall survival (OS), disease-free survival (DFS) and transplant-related mortality (TRM) after HSCT. The study included patients who underwent HSCT, typed at allele resolution level for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci. The analysis performed on the entire patient cohort (N = 232) showed that HLA-B07 supertype positive patients demonstrated decreased incidence of relapse, better OS and DFS in comparison to those negative for HLA-B07 supertype.
View Article and Find Full Text PDFStem Cell Res Ther
December 2024
Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No.107, West Yan Jiang Road, Guangzhou, 510120, Guangdong, China.
Background: Allo-HSCT is a curative therapy for patients with transfusion-dependent thalassemia (TDT). The high incidence of transplant-related complications is becoming an obstacle to safe and effective unrelated donor (URD) transplantation.
Methods: In this retrospective study, we reported the survival outcomes and complications of transplantation in thalassemia patients using a novel regimen consisting of pre-transplantation immunosuppression (PTIS) and modified myeloablative conditioning based on intravenous busulfan, cyclophosphamide, fludarabine, and rabbit anti-human thymocyte immunoglobulin.
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