Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia.

Background: Obecabtagene autoleucel (obe-cel) is an autologous 41BB-ζ anti-CD19 chimeric antigen receptor (CAR) T-cell therapy which uses an intermediate-affinity CAR to reduce toxic effects and improve persistence.

Methods: We conducted a phase 1b-2 multicenter study of obe-cel in adults (≥18 years of age) with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). The main cohort, cohort 2A, included patients with morphologic disease; patients in cohort 2B had measurable residual disease.

Access barriers to anti-CD19+ CART therapy for NHL across a community transplant and cellular therapy network.

We analyzed access barriers to anti-CD19+ chimeric antigen receptor T cells (CARTs) for non-Hodgkin lymphoma (NHL) within a community-based transplant and cell therapy network registry. A total of 357 intended recipients for approved anti-CD19+ CARTs were identified between 2018 to 2022. The median age at referral was 61 years; referral years were 2018 (4%), 2019 (14%), 2020 (18%), 2021 (26%), and 2022 (38%).

The impact of early versus late tocilizumab administration in patients with cytokine release syndrome secondary to immune effector cell therapy.

Introduction: Cytokine release syndrome is a life-threatening hyper-inflammatory state induced by immune effector cell therapy. Anti-interleukin 6-(IL-6) therapy, such as tocilizumab, is the standard treatment for cytokine release syndrome since it reverses symptoms without compromising immune effector cell therapy efficacy. Glucocorticoids are reserved for refractory or severe cytokine release syndrome due to concern for attenuating antitumor activity.

Intrabone transplantation of CD34+ cells with optimized delivery does not enhance engraftment in a rhesus macaque model.

Intrabone (IB) injection of umbilical cord blood has been proposed as a potential mechanism to improve transplant engraftment and prevent graft failure. However, conventional IB techniques produce low retention of transplanted cells in the marrow. To overcome this barrier, we developed an optimized IB (OIB) injection method using low-volume, computer-controlled slow infusion that promotes cellular retention in the marrow.

Upsetting the apple CAR-T (chimeric antigen receptor T-cell therapy) - sustainability mandates USA innovation.

Seldom has a medical advance in cancer therapy been as pivotal as the advent of chimeric antigen receptor (CAR)-T-cell immunotherapy. While the first applications targeted the CD19 antigen on lymphoid malignancies, the incredible specificity of these 'living drugs', curative potential and generalisability to other targets have richly justified their declaration as 2019's breakthrough of the year by Science magazine. Two CAR-T products, Yescarta (axicabtagene ciloleucel) and Kymriah (tisagenlecleucel) were Food and Drug Administration (FDA)-approved in the USA in late 2017, with the FDA commissioner Scott Gottlieb heralding 'a new frontier in medical innovation with the ability to reprogram a patient's own cells to attack a deadly cancer'.

Combination of the low anticoagulant heparin CX-01 with chemotherapy for the treatment of acute myeloid leukemia.

Relapses in acute myelogenous leukemia (AML) are a result of quiescent leukemic stem cells (LSCs) in marrow stromal niches, where they resist chemotherapy. LSCs employ CXCL12/CXCR4 to home toward protective marrow niches. Heparin disrupts CXCL12-mediated sequestration of cells in the marrow.

Acute Kidney Injury in Hematopoietic Cell Transplantation Patients Receiving Vancomycin and Piperacillin/Tazobactam Versus Vancomycin and Cefepime.

Empiric antimicrobials are frequently utilized in the pre-engraftment phase after hematopoietic cell transplantation (HCT). Recent evidence suggests an increased risk of acute kidney injury (AKI) from combination of vancomycin with piperacillin/tazobactam; however, this has not specifically been evaluated in the HCT population. A single-center, retrospective review was conducted from 2011 to 2017 on 110 autologous and 60 allogeneic HCT patients with the primary objective of comparing incidence of AKI for those who received vancomycin with piperacillin/tazobactam versus vancomycin with cefepime in the pre-engraftment phase.

Impact of fluoroquinolone prophylaxis on infectious-related outcomes after hematopoietic cell transplantation.

Background: Patients immediately post-hematopoietic cell transplantation are at high risk for bacteremia. Judicious prophylactic antimicrobial utilization must balance anticipated benefits (reduction infections) versus risk (bacterial resistance, Clostridium difficile) .

Objective: To compare infectious outcomes (primary: incidence bacteremia; secondary: febrile neutropenia, C.

Stable isotopes reveal the effect of trawl fisheries on the diet of commercially exploited species.

Bottom trawling can change food availability for benthivorous demersal species by (i) changing benthic prey composition through physical seabed impacts and (ii) by removing overall benthic consumer biomass increasing the net availability of benthic prey for remaining individuals. Thus trawling may both negatively and positively influence the quantity and quality of food available. Using δ C and δ N we investigated potential diet changes of three commercially exploited species across trawling gradients in the Kattegat (plaice, dab and Norway lobster (Nephrops)) and the Irish Sea (Nephrops).

Allogeneic transplantation using CD34 selected peripheral blood progenitor cells combined with non-mobilized donor T cells for refractory severe aplastic anaemia.

Allogeneic haematopoietic stem cell transplantation is curative for severe aplastic anaemia (SAA) unresponsive to immunosuppressive therapy. To reduce chronic graft-versus-host disease (GVHD), which occurs more frequently after peripheral blood stem cell (PBSC) transplantation compared to bone-marrow transplantation (BMT), and to prevent graft rejection, we developed a novel partial T-cell depleted transplant that infuses high numbers of granulocyte colony-stimulating factor-mobilized CD34 selected PBSCs combined with a BMT-equivalent dose of non-mobilized donor T-cells. Fifteen patients with refractory SAA received cyclophosphamide, anti-thymocyte globulin and fludarabine conditioning, and were transplanted with a median 8 × 10 CD34  cells/kg and 2 × 10 non-mobilized CD3 T-cells/kg from human leucocyte antigen-matched sibling donors.

Treatment of Refractory Anemia with Ring Sideroblasts Associated with Marked Thrombocytosis with Lenalidomide in a Patient Testing Negative for 5q Deletion and V617F and W515K/L Mutations.

Refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T) is a hematologic malignancy that often results in transfusion dependency and a hypercoagulable state. This rare disease currently lacks formal guidelines for treatment; however, various case reports have demonstrated efficacy in the use of lenalidomide. This immunomodulatory drug has shown promise in patients with 5q deletions, with reports of achieving transfusion independence and normalization of platelet counts.

Effect of high-dose plerixafor on CD34 cell mobilization in healthy stem cell donors: results of a randomized crossover trial.

Hematopoietic stem cells can be mobilized from healthy donors using single-agent plerixafor without granulocyte colony-stimulating factor and, following allogeneic transplantation, can result in sustained donor-derived hematopoiesis. However, when a single dose of plerixafor is administered at a conventional 240 μg/kg dose, approximately one-third of donors will fail to mobilize the minimally acceptable dose of CD34 cells needed for allogeneic transplantation. We conducted an open-label, randomized trial to assess the safety and activity of high-dose (480 μg/kg) plerixafor in CD34 cell mobilization in healthy donors.

Conditioning with rabbit versus horse ATG dramatically alters clinical outcomes in identical twins with severe aplastic anemia transplanted with the same allogeneic donor.

Severe aplastic anemia (SAA) is a rare disorder leading to bone marrow failure, which if left untreated, is invariably fatal. Conventional therapies with immunosuppressive therapy or allogeneic hematopoietic stem cell transplantation (HSCT) are highly effective. HSCT can offer a greater outcome in younger patients who have an available HLA match-related donor.

Optimization of intrabone delivery of hematopoietic progenitor cells in a swine model using cell radiolabeling with [89]zirconium.

Intrabone (IB) hematopoietic cell transplantation (HCT) of umbilical cord blood in humans remains experimental and the technique has not been optimized. It is unknown whether hematopoietic progenitor cells (HPCs) injected IB are initially retained in the marrow or rapidly enter into the venous circulation before homing to the marrow. To develop an IB-injection technique that maximizes HPC marrow-retention, we tracked radiolabeled human HPCs following IB-injection into swine.

Long-term outcome of fludarabine-based reduced-intensity allogeneic hematopoietic cell transplantation for debilitating paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis, venous thrombosis, and bone marrow failure. Seventeen patients with debilitating PNH, including 8 who were HLA-alloimmunized, underwent a reduced-intensity allogeneic hematopoietic cell transplantation (HCT). All received cyclophosphamide/fludarabine +/- antithymocyte globulin followed by a granulocyte colony-stimulating factor-mobilized HCT from an HLA-matched relative.

Rapid donor T-cell engraftment increases the risk of chronic graft-versus-host disease following salvage allogeneic peripheral blood hematopoietic cell transplantation for bone marrow failure syndromes.

The risk of graft-rejection after allogeneic hematopoietic cell transplantation using conventional cyclophosphamide-based conditioning is increased in patients with bone marrow failure syndromes (BMFS) who are heavily transfused and often HLA-alloimmunized. Fifty-six patients with BMFS underwent fludarabine-based reduced-intensity conditioning and allogeneic peripheral blood progenitor cell (PBPC) transplantation at a single institution. The conditioning regimen consisted of intravenous cyclophosphamide, fludarabine, and equine antithymocyte globulin.

Posterior segment ophthalmic complications of aplastic anemia.

Three patients with aplastic anemia were evaluated by the ophthalmology service within 2 months of the aplastic anemia diagnosis for bilateral visual loss. The mean age of diagnosis of aplastic anemia was 14.3 years (range: 5 to 19 years) and the mean follow-up was 25 months (range: 15 to 44 months).

Probiotic-associated high-titer anti-B in a group A platelet donor as a cause of severe hemolytic transfusion reactions.

Background: Hemolytic transfusion reactions (HTRs) can occur with transfusion of platelets (PLTs) containing ABO-incompatible plasma. Reported cases have involved group O donors. Two cases of PLT-mediated HTRs associated with the same group A plateletpheresis component, collected from a donor taking high doses of probiotics are reported.

Ferroportin Q248h, dietary iron, and serum ferritin in community African-Americans with low to high alcohol consumption.

Background: Alcohol consumption is associated with increased iron stores. In sub-Saharan Africa, high dietary ionic iron and the ferroportin Q248H allele have also been implicated in iron accumulation. We examined the associations of ferroportin Q248H, alcohol and dietary iron with serum ferritin, aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) concentrations in African-Americans.