Current practices for viability testing of cryopreserved cord blood products: an international survey by the cellular therapy team of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative.

Background: Viability testing is a common practice in laboratories. The goal of this study was to ascertain current laboratory practices internationally for performing viability testing for cryopreserved cord blood (CB) products and glean information about how to standardize the method to improve interlaboratory reproducibility.

Study Design And Methods: A survey to evaluate current laboratory practices for viability testing was designed and distributed internationally.

Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies.

Ravulizumab (ALXN1210), a humanized monoclonal antibody to complement component C5, was engineered from eculizumab to have a substantially longer terminal half-life, permitting longer dosing intervals for paroxysmal nocturnal hemoglobinuria (PNH) treatment. Two phase 1b/2 multicenter open-label studies evaluated efficacy and safety of multiple doses and regimens of ravulizumab in PNH patients naive to complement-inhibitor treatment. Patients in study 103 (n = 13) received ravulizumab 900 mg (lower trough exposure) or 1800 mg every 4 weeks (higher trough exposure); those in study 201 (n = 26) received 1000 mg every 4, 1600 mg every 6, 2400 mg every 8, or 5400 mg every 12 weeks.

Characterization of hospitalized cardiovascular patients with suspected heparin-induced thrombocytopenia.

Background: Little is known about heparin-induced thrombocytopenia (HIT), a pro-thrombotic, potentially life-threatening immune-mediated reaction to heparin exposure, in conservative and interventional cardiovascular medicine.

Hypothesis: The 4T score, validated for prediction of HIT in surgical patients before, is also suitable for assessing HIT probability in cardiovascular patients with unclear thrombocytopenia.

Methods: A total of 403 consecutive patients from our Department of Cardiology, Angiology and Pneumology in whom a HIT screening test was performed between 2009 and 2016 were identified.

Cell therapy induced regeneration of severely atrophied mandibular bone in a clinical trial.

Background: Autologous grafting, despite some disadvantages, is still considered the gold standard for reconstruction of maxillofacial bone defects. The aim of this study was to evaluate bone regeneration using bone marrow-derived mesenchymal stromal cells (MSCs) in a clinical trial, a less invasive approach than autologous bone grafting. This comprehensive clinical trial included subjects with severe mandibular ridge resorption.

Resequencing of four novel alleles with nanopore technology.

Long nanopore reads allow phasing of heterozygous positions but show limitations in sequencing of homopolymers.

Identification of a new exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease.

Chuvash polycythemia is an autosomal recessive form of erythrocytosis associated with a homozygous p.Arg200Trp mutation in the von Hippel-Lindau () gene. Since this discovery, additional mutations have been identified in patients with congenital erythrocytosis, in a homozygous or compound-heterozygous state.

Correlation Between the Transplant Evaluation Rating Scale (TERS) and Medical Outcomes in Living-Donor Kidney Transplant Recipients: A Retrospective Analysis.

Background: Pretransplant psychosocial evaluation of living-donor kidney transplantation (LDKT) candidates identifies recipients with potentially inferior posttransplant outcomes. Rating instruments, based on semi-standardized interviews, help to improve and standardize psychosocial evaluation. The goal of this study was to retrospectively investigate the correlation between the Transplant Evaluation Rating Scale (TERS) and transplant outcome in LDKT recipients.

CD59 deficiency presenting as polyneuropathy and Moyamoya syndrome with endothelial abnormalities of small brain vessels.

CD59 is involved in lymphocyte signal transduction and regulates complement-mediated cell lysis by inhibiting the membrane attack complex. In the cases reported so far, congenital isolated CD59 deficiency was associated with recurrent episodes of hemolytic anemia, peripheral neuropathy, and strokes. Here, we report on a patient from a consanguineous Turkish family, who had a first episode of hemolytic anemia at one month of age and presented at 14 months with acute Guillain-Barré syndrome (GBS).

CD57 identifies T cells with functional senescence before terminal differentiation and relative telomere shortening in patients with activated PI3 kinase delta syndrome.

Premature T-cell immunosenescence with CD57 CD8 T-cell accumulation has been linked to immunodeficiency and autoimmunity in primary immunodeficiencies including activated PI3 kinase delta syndrome (APDS). To address whether CD57 marks the typical senescent T-cell population seen in adult individuals or identifies a distinct population in APDS, we compared CD57 CD8 T cells from mostly pediatric APDS patients to those of healthy adults with similarly prominent senescent T cells. CD57 CD8 T cells from APDS patients were less differentiated with more CD27 CD28 effector memory T cells showing increased PD1 and Eomesodermin expression.

Proteomic definition of human mucosal-associated invariant T cells determines their unique molecular effector phenotype.

Mucosal-associated invariant T cells (MAIT) constitute the most abundant anti-bacterial CD8 T-cell population in humans. MR1/TCR-activated MAIT cells were reported to organize cytotoxic and innate-like responses but knowledge about their molecular effector phenotype is still fragmentary. Here, we have examined the functional inventory of human MAIT cells (CD3 Vα7.

Identification of Elite Neutralizers With Broad and Potent Neutralizing Activity Against Human Cytomegalovirus (HCMV) in a Population of HCMV-Seropositive Blood Donors.

To improve the potency of anti-human cytomegalovirus (HCMV) immunoglobulin preparations, we intended to find elite neutralizers among 9000 HCMV-seropositive blood donors. We identified the top 2.6% neutralizers by use of high-throughput screening and further analyzed the 80 neutralizers with the most effective plasma for strain-independent activity.

Induction of a central memory and stem cell memory phenotype in functionally active CD4 and CD8 CAR T cells produced in an automated good manufacturing practice system for the treatment of CD19 acute lymphoblastic leukemia.

Relapsed/refractory B-precursor acute lymphoblastic leukemia (pre-B ALL) remains a major therapeutic challenge. Chimeric antigen receptor (CAR) T cells are promising treatment options. Central memory T cells (Tcm) and stem cell-like memory T cells (Tscm) are known to promote sustained proliferation and persistence after T-cell therapy, constituting essential preconditions for treatment efficacy.

Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial.

Background: ORTHO-1 is a European, multicentric, first in human clinical trial to prove safety and feasibility after surgical implantation of commercially available biphasic calcium phosphate bioceramic granules associated during surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSC) under good manufacturing practices, in patients with long bone pseudarthrosis.

Methods: Twenty-eight patients with femur, tibia or humerus diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL associated with 5-10 cc of bioceramic granules. Patients were followed up during one year.

The Monoclonal Anti-CD157 Antibody Clone SY11B5, Used for High Sensitivity Detection of PNH Clones on WBCs, Fails to Detect a Common Polymorphic Variant Encoded by BST-1.

Background: CD157, encoded by BST-1, has been described as a useful flow cytometric marker for the analysis of paroxysmal nocturnal hemoglobinuria (PNH) as it is a glycosylphosphatidylinositol (GPI)-linked molecule highly expressed on normal monocytes and neutrophils. We and others observed isolated CD157 signal dropouts during intended PNH analysis. We hypothesize that these negative populations occur due to an antibody failure.

Comparative Analysis of Different Platelet Lysates and Platelet Rich Preparations to Stimulate Tendon Cell Biology: An In Vitro Study.

The poor healing potential of tendons is still a clinical problem, and the use of Platelet Rich Plasma (PRP) was hypothesized to stimulate healing. As the efficacy of PRPs remains unproven, platelet lysate (PL) could be an alternative with its main advantages of storage and characterization before use. Five different blood products were prepared from 16 male donors: human serum, two PRPs (Arthrex, (PRP-ACP); RegenLab (PRP-BCT)), platelet concentrate (apheresis, PC), and PL (freezing-thawing destruction of PC).

Recent advances in understanding the pathogenesis and management of reticular dysgenesis.

Reticular Dysgenesis is a rare immunodeficiency which is clinically characterized by the combination of Severe Combined Immunodeficiency (SCID) with agranulocytosis and sensorineural deafness. Mutations in the gene encoding adenylate kinase 2 (AK2) were identified to cause this phenotype. In this review, we will demonstrate important clinical differences between reticular dysgenesis and other SCID entities and summarize recent concepts in the understanding of the pathophysiology of the disease and the management strategies for this difficult condition.

Optimal Storage Conditions for Apheresis Research (OSCAR): a Biomedical Excellence for Safer Transfusion (BEST) Collaborative study.

Background: Cell therapy products are often stored and transported between sites. The aim of this study was to determine the effect of storage temperature, solution, and cell concentration on nonmobilized, peripheral blood-derived mononuclear cells (MNCs).

Study Design And Methods: This was a multicenter prospective study involving healthy volunteers who underwent nonmobilized MNC collection by apheresis.

An international investigation into AB plasma administration in hospitals: how many AB plasma units were infused? The HABSWIN study.

Background: Typical practice is to transfuse group-specific plasma units; however, there are situations where group AB plasma (universal donor) is issued to group A, B, or O recipients. If demand for group AB plasma exceeds collections, there is potential for shortage. This project explored the patterns of group AB plasma utilization at hospitals around the world.

Corrigendum: Clinical and Molecular Heterogeneity of RTEL1 Deficiency.

[This corrects the article on p. 449 in vol. 8, PMID: 28507545.

Genome-wide Mapping of Off-Target Events in Single-Stranded Oligodeoxynucleotide-Mediated Gene Repair Experiments.

Short single-stranded oligodeoxynucleotides are versatile molecular tools used in different applications. They enable gene repair and genome editing, and they are central to the antisense technology. Because the usability of single-stranded oligodeoxynucleotides depends on their efficiencies, as well as their specificities, analyzing their genotoxic off-target activities is important.

An international investigation into O red blood cell unit administration in hospitals: the GRoup O Utilization Patterns (GROUP) study.

Background: Transfusion of group O blood to non-O recipients, or transfusion of D- blood to D+ recipients, can result in shortages of group O or D- blood, respectively. This study investigated RBC utilization patterns at hospitals around the world and explored the context and policies that guide ABO blood group and D type selection practices.

Study Design And Methods: This was a retrospective study on transfusion data from the 2013 calendar year.

Changes of Bone Turnover Markers in Long Bone Nonunions Treated with a Regenerative Approach.

In this clinical trial, we investigated if biochemical bone turnover markers (BTM) changed according to the progression of bone healing induced by autologous expanded MSC combined with a biphasic calcium phosphate in patients with delayed union or nonunion of long bone fractures. Bone formation markers, bone resorption markers, and osteoclast regulatory proteins were measured by enzymatic immunoassay before surgery and after 6, 12, and 24 weeks. A satisfactory bone healing was obtained in 23 out of 24 patients.

Bone marrow failure unresponsive to bone marrow transplant is caused by mutations in .

We report 5 individuals in 3 unrelated families with severe thrombocytopenia progressing to trilineage bone marrow failure (BMF). Four of the children received hematopoietic stem cell transplants and all showed poor graft function with persistent severe cytopenias even after repeated transplants with different donors. Exome and targeted sequencing identified mutations in the gene encoding thrombopoietin (): THPO R99W, homozygous in affected children in 2 families, and THPO R157X, homozygous in the affected child in the third family.