Development of an Unrelated Donor Selection Score Predictive of Survival after HCT: Donor Age Matters Most.

Donor factors, in addition to HLA matching status, have been associated with recipient survival in unrelated donor (URD) hematopoietic cell transplantation (HCT); however, there is no hierarchical algorithm that weights the characteristics of individual donors against each other in a quantitative manner to facilitate donor selection. The goal of this study was to develop and validate a donor selection score that prioritizes donor characteristics associated with better survival in 8/8 HLA-matched URDs. Two separate patient/donor cohorts, the first receiving HCT between 1999 and 2011 (n = 5952, c1), and the second between 2012 and 2014 (n = 4510, c2) were included in the analysis.

Identification of the novel allele, HLA-B*14:56, in a Brazilian individual.

Novel allele, HLA-B*14:56, generated by a gene conversion event was identified in a Brazilian individual.

A novel allele, HLA-B*51:220, identified in an individual from south of Brazil.

Novel allele, HLA-B*51:220 generated by a gene conversion event was identified in a Brazilian individual.

Cord blood transplantation recapitulates fetal ontogeny with a distinct molecular signature that supports CD4 T-cell reconstitution.

Omission of in vivo T-cell depletion promotes rapid, thymic-independent CD4-biased T-cell recovery after cord blood transplant. This enhanced T-cell reconstitution differs from that seen after stem cell transplant from other stem cell sources, but the mechanism is not known. Here, we demonstrate that the transcription profile of naive CD4 T cells from cord blood and that of lymphocytes reconstituting after cord blood transplantation is similar to the transcription profile of fetal CD4 T cells.

Single molecule real-time DNA sequencing of HLA genes at ultra-high resolution from 126 International HLA and Immunogenetics Workshop cell lines.

The hyperpolymorphic HLA genes play important roles in disease and transplantation and act as genetic markers of migration and evolution. A panel of 107 B-lymphoblastoid cell lines (B-LCLs) was established in 1987 at the 10th International Histocompatibility Workshop as a resource for the immunogenetics community. These B-LCLs are well characterised and represent diverse ethnicities and HLA haplotypes.

HFE gene polymorphism defined by sequence-based typing of the Brazilian population and a standardized nomenclature for HFE allele sequences.

The HFE molecule controls iron uptake from gut, and defects in the molecule have been associated with iron overload, particularly in hereditary hemochromatosis. The HFE gene including both coding and boundary intronic regions were sequenced in 304 Brazilian individuals, encompassing healthy individuals and patients exhibiting hereditary or acquired iron overload. Six sites of variation were detected: (1) H63D C>G in exon 2, (2) IVS2 (+4) T>C in intron 2, (3) a C>G transversion in intron 3, (4) C282Y G>A in exon 4, (5) IVS4 (-44) T>C in intron 4, and (6) a new guanine deletion (G>del) in intron 5, which were used for haplotype inference.

Umbilical Cord Blood Cytomegalovirus Serostatus Does Not Have an Impact on Outcomes of Umbilical Cord Blood Transplantation for Acute Leukemia.

Several studies have reported an impact of adult hematopoietic stem cell donor cytomegalovirus (CMV) serostatus on allogeneic hematopoietic cell transplantation outcomes. Limited data, however, are available on the impact of cord blood unit (CBU) CMV serostatus on allogeneic umbilical cord blood transplantation (UCBT) outcomes. We analyzed, retrospectively, the impact of CBU CMV serostatus on relapse incidence (RI) and 2-year nonrelapse mortality (NRM) of single-unit CBU transplantation for acute leukemia.

Distinguishing functional polymorphism from random variation in the sequences of >10,000 HLA-A, -B and -C alleles.

HLA class I glycoproteins contain the functional sites that bind peptide antigens and engage lymphocyte receptors. Recently, clinical application of sequence-based HLA typing has uncovered an unprecedented number of novel HLA class I alleles. Here we define the nature and extent of the variation in 3,489 HLA-A, 4,356 HLA-B and 3,111 HLA-C alleles.

TypeLoader: A fast and efficient automated workflow for the annotation and submission of novel full-length HLA alleles.

Recent years have seen a rapid increase in the discovery of novel allelic variants of the human leukocyte antigen (HLA) genes. Commonly, only the exons encoding the peptide binding domains of novel HLA alleles are submitted. As a result, the IPD-IMGT/HLA Database lacks sequence information outside those regions for the majority of known alleles.

Natural killer cells differentiated in vitro from cord blood CD34 cells are more advantageous for use as an immunotherapy than peripheral blood and cord blood natural killer cells.

Background Aims: Natural killer (NK) cells have the potential to become a successful immunotherapy as they can target malignant cells without being direct effectors of graft-versus-host disease. Our group has previously shown that large numbers of functional NK cells can be differentiated in vitro from umbilical cord blood (CB) CD34 cells. To produce a clinically relevant and effective immunotherapy, we hypothesized that it is essential that the NK cells are able to proliferate and persist in vivo while maintaining an optimal activation status and killing capacity.

Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.

In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem-cell-derived organoid cultures to generate three-dimensional cultures of normal and decidualized human endometrium.

Umbilical Cord Blood Natural Killer Cells, Their Characteristics, and Potential Clinical Applications.

Natural killer (NK) cells are lymphocytes of the innate immune system able to kill different targets such as cancer cells and virally infected cells without prior activation making then attractive candidates for cancer immunotherapy. Umbilical cord blood (UCB) has become a source of hematopoietic stem cells for transplantation but as we gain a better understanding of the characteristics of each immune cell that UCB contains, we will also be able to develop new cell therapies for cancer. In this review, we present what is currently known of the phenotype and functions of UCB NK cells and how these cells could be used in the future for cancer immunotherapy.

Identification of a novel HLA-A*02:01:01 variant, HLA-A*02:01:01:09, in a Taiwanese bone marrow donor.

An intronic mutation in intron 3 of A*02:01:01:01 leads to the formation of A*02:01:01:09.

Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis.

Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute myeloid leukemia, but detection methodologies and results vary widely. We performed a systematic review and meta-analysis evaluating the prognostic role of minimal residual disease detected by polymerase chain reaction or multiparametric flow cytometry before transplant. We identified 19 articles published between January 2005 and June 2016 and extracted hazard ratios for leukemia-free survival, overall survival, and cumulative incidences of relapse and non-relapse mortality.

Identification of the novel HLA-B*39:01:01:04 allele in a Chinese individual by sequence-based typing.

The new HLA-B*39:01:01:04 allele differs from HLA-B*39:01:01 by a C → T substitution in intron 1.

A dispermic chimerism detected in a Taiwanese potential unrelated hematopoietic stem cell donor.

Chimerism is defined as the presence of 2 or more than 1 genetically distinct cell populations in an organism. Dispermic chimeras are derived from the fertilization of 1 or 2 matured nuclei by 2 sperms. We here report detection of a healthy and phenotypically normal female with normal ABO red blood cell typing in whom dispermic chimerism was suspected after 3 alleles were identified at multiple human leukocyte antigen (HLA) loci using molecular HLA analysis.