Tabelecleucel for EBV+ PTLD after allogeneic HCT or SOT in a multicenter expanded access protocol.

Patients with Epstein-Barr virus (EBV)-positive posttransplant lymphoproliferative disease (EBV+ PTLD) in whom initial treatment fails have few options and historically low median overall survival (OS) of 0.7 months after allogeneic hematopoietic cell transplant (HCT) and 4.1 months after solid organ transplant (SOT).

Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE): a phase 3, multicentre, open-label trial.

Background: Survival in Epstein-Barr virus (EBV)-positive post-transplant lymphoproliferative disease following haematopoietic stem-cell transplant (HSCT) or solid organ transplant (SOT) is poor after failure of initial therapy, indicating an urgent need for therapies for this ultra-rare disease. With recent EU marketing authorisation, tabelecleucel is the first off-the-shelf, allogeneic, EBV-specific T-cell immunotherapy to receive approval for treatment of relapsed or refractory EBV-positive post-transplant lymphoproliferative disease. We aimed to determine the clinical benefit of tabelecleucel in patients with relapsed or refractory EBV-positive post-transplant lymphoproliferative disease following HSCT or SOT.

Romosozumab in Postmenopausal Korean Women with Osteoporosis: A Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study.

Background: This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmenopausal women with osteoporosis.

Methods: Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤-2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months.

Correction to: Relationship between P1NP, a biochemical marker of bone turnover, and bone mineral density in patients transitioned from alendronate to romosozumab or teriparatide: a post hoc analysis of the STRUCTURE trial.

In the original publication of the article, the last row of Table 1 was published incorrectly as "Serum P1NP (μmol/L), median (IQR) : Romosozumab, 25 (18, 34); Teriparatide, 25 (20, 33)". The correct row should be read as "Serum P1NP (μg/L), median (IQR) : Romosozumab, 25 (18, 34); Teriparatide, 25 (20, 33)".

Relationship between P1NP, a biochemical marker of bone turnover, and bone mineral density in patients transitioned from alendronate to romosozumab or teriparatide: a post hoc analysis of the STRUCTURE trial.

Introduction: Procollagen type I N-terminal propeptide (P1NP), a bone formation marker, reportedly predicts bone mineral density (BMD) response to teriparatide treatment in treatment-naive patients with osteoporosis. Results from a randomized, phase 3, open-label, active-controlled trial- STRUCTURE-showed that in patients previously treated with bisphosphonates, romosozumab led to gains in hip BMD, which were not observed with teriparatide. This post hoc analysis investigated the comparative utility of early changes in P1NP in predicting BMD response in patients who participated in the STRUCTURE trial, which enrolled patients who switched treatment from bisphosphonates to romosozumab/teriparatide.

Increased bone mineral density for 1 year of romosozumab, vs placebo, followed by 2 years of denosumab in the Japanese subgroup of the pivotal FRAME trial and extension.

Unlabelled: Romosozumab, which binds sclerostin, rebuilds the skeletal foundation before transitioning to antiresorptive treatment. This subgroup analysis of an international, randomized, double-blind study in postmenopausal women with osteoporosis showed efficacy and safety outcomes for romosozumab followed by denosumab in Japanese women were generally consistent with those for the overall population.

Purpose: In the international, randomized, double-blind, phase 3 FRActure study, in postmenopausal woMen with ostEoporosis (FRAME; NCT01575834), romosozumab followed by denosumab significantly improved bone mineral density (BMD) and reduced fracture risk.

One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study.

Romosozumab, a humanized monoclonal antibody that binds and inhibits sclerostin, has the dual effect of increasing bone formation and decreasing bone resorption. As previously reported in the pivotal FRActure study in postmenopausal woMen with ostEoporosis (FRAME), women with a T-score of ≤ -2.5 at the total hip or femoral neck received subcutaneous placebo or romosozumab once monthly for 12 months, followed by open-label subcutaneous denosumab every 6 months for an additional 12 months.

Current unmet needs in renal transplantation: a review of challenges and therapeutics.

While has been considerable progress in the short-term outcomes following renal transplantation over the last several decades, minimal gains have been made with regards to long-term graft function and patient survival (1). The lack of long-term gains has been attributed to factors such as antibody mediated rejection (AMR), chronic allograft nephropathy (CAN), and toxicity to the allograft secondary to immunosuppression. Ischemia reperfusion injury (IRI) is also thought to contribute to poor long-term graft function, and its impact on patient and graft outcomes will likely expand with the increasing use of marginal kidneys secondary to organ shortages.

Effect of high-dose intravenous immunoglobulin on anti-HLA antibodies in sensitized kidney transplant candidates.

Limited data exist on the effect of intravenous immunoglobulin (IVIg) on anti-HLA antibodies as determined by solid-phase assays. We reviewed our experience treating sensitized wait-listed kidney transplant recipients with IVIg as a method for desensitization and report our results utilizing Luminex single antigen (LSA) bead assay to quantify antibody reactivity (MFI). Fifteen patients with a cPRA > 40% received 2 g/kg IVIg per month for four months or until transplanted.

Transplant immunology for non-immunologist.

Transplantation is the treatment of choice for end-stage kidney, heart, lung, and liver disease. Short-term outcomes in solid-organ transplantation are excellent, but long-term outcomes remain suboptimal. Advances in immune suppression and human leukocyte antigen matching techniques have reduced the acute rejection rate to <10%.

Anticardiac myosin immunity and chronic allograft vasculopathy in heart transplant recipients.

Chronic allograft vasculopathy (CAV) contributes to heart transplant failure, yet its pathogenesis is incompletely understood. Although cellular and humoral alloimmunity are accepted pathogenic mediators, animal models suggest that T cells and Abs reactive to graft-expressed autoantigens, including cardiac myosin (CM), could participate. To test the relationship between CAV and anti-CM autoimmunity in humans, we performed a cross-sectional study of 72 heart transplant recipients: 40 with CAV and 32 without.

Antibodies reactive to non-HLA antigens in transplant glomerulopathy.

Although T and B cell alloimmunity contribute to transplant injury, autoimmunity directed at kidney-expressed, non-HLA antigens may also participate. Because the specificity, prevalence, and importance of antibodies to non-HLA antigens in late allograft injury are poorly characterized, we used a protein microarray to compare antibody repertoires in pre- and post-transplant sera from several cohorts of patients with and without transplant glomerulopathy. Transplantation routinely induced changes in antibody repertoires, but we did not identify any de novo non-HLA antibodies common to patients with transplant glomerulopathy.

T-cell immune monitoring in organ transplantation.

Chronic allograft injury remains the leading cause of graft loss despite improvements in immunosuppression, clinical risk stratification, and state-of-the-art antibody testing. Emerging results indicate that T-cell immune monitoring by cytokine enzyme-linked immunosorbent spot, as part of a comprehensive risk assessment platform, has the potential to guide decision making and improve outcomes after transplantation.

Differential outcomes in 3 types of acute antibody-mediated rejection.

Introduction: The aim of this study is to investigate the prevalence, predictors, and clinical outcomes of acute antibody-mediated rejection (AAMR).

Methods: Retrospective analysis of 833 adult patients who received kidney transplantation between 1/1/2001 and 8/15/2007.

Results: The prevalence of AAMR and acute cellular rejection was 2% and 8.

T-cell immune monitoring in organ transplantation.

Purpose Of Review: Chronic injury and late allograft loss remain major causes of morbidity in clinical transplantation. Biomarkers that can reliably assess the risk of posttransplant complications are required to direct and individualize therapy aimed at prolonging graft survival and improving patient health. The purpose of this review is to provide a framework for understanding how to use biomarkers in the context of clinical transplantation and to summarize current data on available noninvasive cellular-based immune monitoring methods to predict transplant outcome.

Addition of plasmapheresis decreases the incidence of acute antibody-mediated rejection in sensitized patients with strong donor-specific antibodies.

Background And Objectives: The objective of this study was to investigate the effects of desensitization protocols using intravenous Ig with or without plasmapheresis in patients with donor-specific anti-HLA antibodies on prevention of antibody-mediated rejection and downregulation of donor-specific antibodies.

Design, Setting, Participants, & Measurements: Thirty-five complement-dependent cytotoxicity T cell cross-match-negative but complement-dependent cytotoxicity B cell and/or flow cytometry cross-match-positive kidney transplant recipients were treated with high-dosage intravenous Ig plus Thymoglobulin induction treatment. Donor-specific antibody strength was stratified as strong, medium, or weak by Luminex flow beads.

Preemptive kidney transplantation in patients with diabetes mellitus.

Kidney transplantation is the most preferred treatment for end-stage renal disease because it improves not only the patient's survival compared with dialysis, but also the quality of life. Preemptive transplantation is transplantation performed prior to the initiation of renal dialysis. Recent observational studies have shown increased patient and graft survival with preemptive transplantation, compared to patients receiving transplantation after the initiation of dialysis.

Transplant glomerulopathy may occur in the absence of donor-specific antibody and C4d staining.

Background And Objectives: Transplant glomerulopathy (TGP) has been proposed to be a component of chronic antibody-mediated rejection (AMR). We have studied 36 patients with TGP and 51 patients with chronic allograft nephropathy (CAN) but without TGP for C4d staining and donor-specific anti-HLA antibodies (DSA) to investigate the alloantibody-mediated mechanisms.

Design, Setting, Participants, & Measurements: Allograft biopsies were stained with C4d staining and DSAs were studied by Luminex Flow Beads.

Relationship of homocysteine with cardiovascular disease and blood pressure.

Elevated plasma homocysteine (Hcy) concentration is considered a risk factor for cardiovascular disease and may also be associated with hypertension. Although links have been established between hyperhomocysteinemia and elevated risk for cardiovascular events, the precise role of plasma Hcy in cardiovascular disease is unclear. Plasma Hcy increases with aging and is associated with other health-related behaviors, including smoking and diet patterns.

Plasma homocysteine concentration and blood pressure in young adult African Americans.

Background: An association of plasma homocysteine concentration ([Hcy]) with cardiovascular events has been described, but the role of [Hcy] in the early phase of cardiovascular disease is uncertain. The purpose of this study was to determine whether [Hcy] is related to blood pressure (BP) or other risk factors in African Americans, a population at high risk for cardiovascular disease.

Methods: This cross-sectional study was conducted on a sample of premenopausal African American women (N = 119) and men (N = 56), 30 to 40 years of age.