Publications by authors named "Laura Johnston"

129 Publications

Comparison of polynomial fitting versus single time point analysis of ECIS data for barrier assessment.

Physiol Rep 2021 Oct;9(19):e14983

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Electrical cell-substrate impedance sensing (ECIS) is an in vitro methodology for measuring the barrier integrity of a variety of cell types, including pulmonary endothelial cells. These experiments are frequently used for in vitro assessment of lung injury. The data derived from ECIS experiments consists of repeated measures of resistance across an endothelial monolayer. As such, these data reflect the dynamic changes in electrical resistance that occur over time. Currently methodologies for assessing ECIS data rely on single point assessments of barrier function, such as the maximal drop in trans-endothelial electrical resistance (TER ). However, this approach ignores the myriad of changes in resistance that occur before and after the TER data point. Herein, we utilize polynomial curve fitting on experimentally generated ECIS data, thus allowing for comparing ECIS experiments by examining the mean polynomial coefficients between groups. We show that polynomial curves accurately fit a variety of ECIS data, and that concordance between TER and coefficient analysis varies by type of stimulus, suggesting that TER differences may not always correlate with a significant difference in the overall shape of the ECIS profile. Lastly, we identify factors that impact coefficient values obtained in our analyses, including the length of time devoted to baseline measurements before addition of stimuli. Polynomial coefficient analysis is another tool that can be used for more comprehensive interrogation of ECIS data to better understand the biological underpinnings that lead to changes in barrier dysfunction in vitro.
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http://dx.doi.org/10.14814/phy2.14983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488550PMC
October 2021

PDE9A deficiency does not prevent chronic-hypoxic pulmonary hypertension in mice.

Physiol Rep 2021 Sep;9(18):e15057

Division of Pulmonary and Critical Care Medicine Pulmonary, Johns Hopkins University, Baltimore, Maryland, USA.

Inhibition of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterases (PDEs) is a cornerstone of pulmonary arterial hypertension (PAH)-specific therapy. PDE9A, expressed in the heart and lung tissue, has the highest affinity for cGMP of all known PDEs. PDE9A deficiency protects mice against chronic left ventricular (LV) pressure overload via increased natriuretic peptide (NP)-dependent cGMP signaling. Chronic-hypoxic pulmonary hypertension (CH-PH) is a model of chronic right ventricular (RV) pressure overload, and previous studies have demonstrated a protective role for NPs in the murine model. Therefore, we hypothesized that PDE9A deficiency would promote NP-dependent cGMP signaling and prevent RV remodeling in the CH-PH model, analogous to findings in the LV. We exposed wild-type and PDE9A-deficient (Pde9a ) C57BL/6 mice to CH-PH for 3 weeks. We measured RV pressure, hypertrophy, and levels of lung and RV cGMP, PDE9A, PDE5A, and phosphorylation of the protein kinase G substrate VASP (vasodilatory-stimulated phosphoprotein) after CH-PH. In wild-type mice, CH-PH was associated with increased circulating ANP and lung PDE5A, but no increase in cGMP, PDE9A, or VASP phosphorylation. Downstream effectors of cGMP were not increased in Pde9a mice exposed to CH-PH compared with Pde9a littermates, and CH-PH induced increases in RV pressure and hypertrophy were not attenuated in knockout mice. Taken together, these findings argue against a prominent role for PDE9A in the murine CH-PH model.
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http://dx.doi.org/10.14814/phy2.15057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474007PMC
September 2021

Incidence and Risk Factors Associated with Bleeding and Thrombosis Following Chimeric Antigen Receptor T Cell Therapy.

Blood Adv 2021 Sep 14. Epub 2021 Sep 14.

Stanford University, Stanford, California, United States.

Bleeding and thrombotic events are an emerging toxicity associated with chimeric antigen receptor (CAR) therapies. To determine their incidence, we retrospectively analyzed consecutive adult patients (n=127) with large B-cell lymphoma (LBCL) or B-cell acute lymphoblastic leukemia (B-ALL) treated between 2017-2020 with axicabtagene ciloleucel (axi-cel) (N=89) or a bispecific CD19/CD22 CAR (N=38). 12 (9.4%) and 8 (6.3%) patients developed bleeding and thrombosis within first 3 months, respectively. In the axi-cel subgroup, these occurred in 11.2% and 6.7%, respectively. Bleeding occurred between days 8-30 (median 17.5), and thrombosis between days 2-91 (median 29). Bleeding sites included genitourinary (N=6), soft tissue (N=2), intracranial (N=2), gastrointestinal (N=1), pulmonary (N=1), and were associated with features of consumptive coagulopathy. On univariate analysis, patients with bleeding were older (median 72 vs. 60 yrs, P<0.01), had lower baseline platelets (86 vs. 178 K/uL, P<0.01), lower platelet nadir after CAR-T (median 17.5 vs. 48 K/uL; P<0.01), lower fibrinogen nadir (median 122 vs. 340 ug/mL; P<0.01) and elevated LDH (P=0.01). ICANS grade ≥3 was associated with increased bleeding (50% vs. 15%; P=0.01), thrombosis (50% vs. 16%; P=0.04), PT prolongation, hypofibrinogenemia and elevated D-dimer. A paucity of events limited multivariate analysis, however low pre-treatment platelets were associated with bleeding in a multivariate logistic regression model. Patients with thrombocytopenia or severe ICANS are at increased risk of bleeding complications and should be closely monitored particularly within the first month after CAR therapy. Future studies in larger cohorts should assess risk factors for systemic coagulopathies in CAR-T therapy, including their association with neurotoxicity.
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http://dx.doi.org/10.1182/bloodadvances.2021004716DOI Listing
September 2021

Panel Optimization for High-Dimensional Immunophenotyping Assays Using Full-Spectrum Flow Cytometry.

Curr Protoc 2021 Sep;1(9):e222

Malaghan Institute of Medical Research, Wellington, New Zealand.

Technological advancements in fluorescence flow cytometry and an ever-expanding understanding of the complexity of the immune system have led to the development of large flow cytometry panels reaching up to 43 colors at the single-cell level. However, as panel size and complexity increase, so too does the detail involved in designing and optimizing successful high-quality panels fit for downstream high-dimensional data analysis. In contrast to conventional flow cytometers, full-spectrum flow cytometers measure the entire emission spectrum of each fluorophore across all lasers. This allows for fluorophores with very similar emission maxima but unique overall spectral fingerprints to be used in conjunction, enabling relatively straightforward design of larger panels. Although a protocol for best practices in full-spectrum flow cytometry panel design has been published, there is still a knowledge gap in going from the theoretically designed panel to the necessary steps required for panel optimization. Here, we aim to guide users through the theory of optimizing a high-dimensional full-spectrum flow cytometry panel for immunophenotyping using comprehensive step-by-step protocols. These protocols can also be used to troubleshoot panels when issues arise. A practical application of this approach is exemplified with a 24-color panel designed for identification of conventional T-cell subsets in human peripheral blood. © 2021 Malaghan Institute of Medical Research, Cytek Biosciences. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Preparation and evaluation of optimal spectral reference controls Support Protocol 1: Antibody titration Support Protocol 2: Changing instrument settings Basic Protocol 2: Unmixing evaluation of fully stained sample Basic Protocol 3: Evaluation of marker resolution Support Protocol 3: Managing heterogeneous autofluorescence Basic Protocol 4: Assessment of data quality using expert gating and dimensionality reduction algorithms.
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http://dx.doi.org/10.1002/cpz1.222DOI Listing
September 2021

Concordance of peripheral blood and bone marrow measurable residual disease in adult acute lymphoblastic leukemia.

Blood Adv 2021 08;5(16):3147-3151

Division of Blood and Marrow Transplantation.

Monitoring of measurable residual disease (MRD) is essential to the management of acute lymphoblastic leukemia (ALL) and is typically performed through repeated bone marrow (BM) assessments. Using a next-generation sequencing (NGS) MRD platform, we performed a prospective observational study evaluating the correlation between peripheral blood (PB) and BM MRD in adults with ALL receiving cellular therapies (hematopoietic cell transplantation [HCT] and chimeric antigen receptor T-cell [CAR-T] therapies). Among the study cohort (N = 69 patients; 126 paired PB/BM samples), we found strong correlation between PB and BM MRD (r = 0.87; P < .001), with a sensitivity and specificity of MRD detection in the PB of 87% and 90%, respectively, relative to MRD in the BM. MRD became detectable in the PB in 100% of patients who subsequently relapsed following HCT, with median time from MRD+ to clinical relapse of 90 days, and in 85% of patients who relapsed following CAR T, with median time from MRD+ to clinical relapse of 60 days. In adult patients with ALL undergoing cellular therapies, we demonstrate strong concordance between NGS-based MRD detected in the PB and BM. Monitoring of ALL MRD in the PB appears to be an adequate alternative to frequent invasive BM evaluations in this clinical setting.
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http://dx.doi.org/10.1182/bloodadvances.2021004234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405199PMC
August 2021

CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial.

Nat Med 2021 08 26;27(8):1419-1431. Epub 2021 Jul 26.

Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.

Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten of 16 patients with large B cell lymphoma (LBCL) with progressive disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated with progressive disease. To prevent relapse with CD19 or CD19 disease, we tested a bispecific CAR targeting CD19 and/or CD22 (CD19-22.BB.z-CAR) in a phase I clinical trial ( NCT03233854 ) of adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) and LBCL. The primary end points were manufacturing feasibility and safety with a secondary efficacy end point. Primary end points were met; 97% of products met protocol-specified dose and no dose-limiting toxicities occurred during dose escalation. In B-ALL (n = 17), 100% of patients responded with 88% minimal residual disease-negative complete remission (CR); in LBCL (n = 21), 62% of patients responded with 29% CR. Relapses were CD19 in 50% (5 out of 10) of patients with B-ALL and 29% (4 out of 14) of patients with LBCL but were not associated with CD22 disease. CD19/22-CAR products demonstrated reduced cytokine production when stimulated with CD22 versus CD19. Our results further implicate antigen loss as a major cause of CAR T cell resistance, highlight the challenge of engineering multi-specific CAR T cells with equivalent potency across targets and identify cytokine production as an important quality indicator for CAR T cell potency.
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http://dx.doi.org/10.1038/s41591-021-01436-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363505PMC
August 2021

Standardizing Definitions of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, and Donor Chimerism in Allogeneic Hematopoietic Cell Transplantation: A Report on Behalf of the American Society for Transplantation and Cellular Therapy.

Transplant Cell Ther 2021 08;27(8):642-649

West Virginia University, Morgantown, West Virginia.

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and conditioning intensity, among other variables. To address these contemporary challenges, we surveyed a panel of allo-HCT experts in an attempt to standardize these definitions. We analyzed survey responses from adult and pediatric transplantation physicians separately. Consensus was achieved for definitions of neutrophil and platelet recovery, graft rejection, graft failure, poor graft function, and donor chimerism, but not for delayed engraftment. Here we highlight the complexities associated with the management of mixed donor chimerism in malignant and nonmalignant hematologic diseases, which remains an area for future research. We recognize that there are multiple other specific, and at times complex, clinical scenarios for which clinical management must be individualized.
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http://dx.doi.org/10.1016/j.jtct.2021.04.007DOI Listing
August 2021

Outcomes after delayed and second autologous stem cell transplant in patients with relapsed multiple myeloma.

Bone Marrow Transplant 2021 Jun 23. Epub 2021 Jun 23.

Department of Medicine, Stanford University, Stanford, CA, USA.

We evaluated the outcomes of 168 patients undergoing delayed or second autologous stem cell transplant (ASCT) for relapsed multiple myeloma (MM) from 2010 to 2019. Overall, 21% (n = 35) patients had received a prior transplant and 69% (n = 116) underwent transplant at first relapse. Overall, 27% patients had high-risk cytogenetics and 15% had ISS stage III disease. Stem cell collection was performed after relapse in 72% and 35% of patients received maintenance therapy. Median PFS from salvage treatment and transplant were 28 and 19 months, respectively. Median OS from salvage treatment and transplant was 69 and 55 months. Multivariate analysis revealed that ASCT in first relapse was associated with superior PFS (HR 0.63, p = 0.03) and OS (HR 0.59, p = 0.04) compared to later lines of therapy. In addition, PFS of ≥36 months with prior therapy was associated with improved PFS (HR 0.62, p = 0.04) and OS (HR 0.41, p = 0.01). Ninety-five patients underwent delayed transplant at first relapse, median PFS and OS from start of therapy was 30 and 69 months, and median OS from diagnosis was 106 months. These data may serve as a guide when counseling patients undergoing ASCT for relapsed MM and provide a benchmark in designing clinical trials of transplantation/comparative treatments for relapsed MM.
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http://dx.doi.org/10.1038/s41409-021-01371-1DOI Listing
June 2021

Fifteen-minute consultation: oral ulceration in children.

Arch Dis Child Educ Pract Ed 2021 May 27. Epub 2021 May 27.

Paediatric Dentistry, University of Birmingham, Birmingham, UK.

Objective: To review common presentation of oral ulcers in children and discuss management of symptoms and subsequent investigation.

Conclusion: Although a common presentation in children, diagnosis can be challenging. Thorough history taking is critical towards diagnosis and supports signposting to relevant specialities. Clinicians should be able to support first-line symptomatic management of oral ulceration.
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http://dx.doi.org/10.1136/archdischild-2021-321597DOI Listing
May 2021

Head-to-head Comparison of Qualitative Radiologist Assessment With Automated Quantitative Computed Tomography Analysis for Bronchiolitis Obliterans Syndrome After Hematopoietic Cell Transplantation.

J Thorac Imaging 2021 May 12. Epub 2021 May 12.

Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine Department of Radiology, Stanford University School of Medicine Department of Medicine, Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA.

Purpose: Computed tomography (CT) findings of bronchiolitis obliterans syndrome (BOS) can be nonspecific and variable. This study aims to measure the incremental value of automated quantitative lung CT analysis to clinical CT interpretation. A head-to-head comparison of quantitative CT lung density analysis by parametric response mapping (PRM) with qualitative radiologist performance in BOS diagnosis was performed.

Materials And Methods: Inspiratory and end-expiratory CTs of 65 patients referred to a post-bone marrow transplant lung graft-versus-host-disease clinic were reviewed by 3 thoracic radiologists for the presence of mosaic attenuation, centrilobular opacities, airways dilation, and bronchial wall thickening. Radiologists' majority consensus diagnosis of BOS was compared with automated PRM air trapping quantification and to the gold-standard diagnosis of BOS as per National Institutes of Health (NIH) consensus criteria.

Results: Using a previously established threshold of 28% air trapping on PRM, the diagnostic performance for BOS was as follows: sensitivity 56% and specificity 94% (area under the receiver operator curve [AUC]=0.75). Radiologist review of inspiratory CT images alone resulted in a sensitivity of 80% and a specificity of 69% (AUC=0.74). When radiologists assessed both inspiratory and end-expiratory CT images in combination, the sensitivity was 92% and the specificity was 59% (AUC=0.75). The highest performance was observed when the quantitative PRM report was reviewed alongside inspiratory and end-expiratory CT images, with a sensitivity of 92% and a specificity of 73% (AUC=0.83).

Conclusions: In the CT diagnosis of BOS, qualitative expert radiologist interpretation was noninferior to quantitative PRM. The highest level of diagnostic performance was achieved by the combination of quantitative PRM measurements with qualitative image feature assessments.
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http://dx.doi.org/10.1097/RTI.0000000000000595DOI Listing
May 2021

Stem Cell Mobilization in Multiple Myeloma: Comparing Safety and Efficacy of Cyclophosphamide +/- Plerixafor versus Granulocyte Colony-Stimulating Factor +/- Plerixafor in the Lenalidomide Era.

Transplant Cell Ther 2021 07 26;27(7):590.e1-590.e8. Epub 2021 Apr 26.

Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California. Electronic address:

Growth factor and chemotherapy-based stem cell mobilization strategies are commonly used to treat patients with multiple myeloma. We retrospectively compared 398 patients mobilized between 2017 and 2020 using either cyclophosphamide (4 g/m) plus granulocyte colony-stimulating factor (G-CSF) or G-CSF alone, with on demand plerixafor (PXF) in both groups. Although total CD34 yield was higher after chemomobilization compared with G-CSF +/- PXF (median, 13.6 × 10/kg versus 4.4 × 10/kg; P < .01), achievement of ≥2 × 10 CD34 cells (95% versus 93.7%; P = .61) and rates of mobilization failure (5% versus 6.3%; P = .61) were similar. Fewer patients required PXF with chemomobilization (12.3% versus 49.5%; P < .01), and apheresis sessions were fewer (median, 1 [range, 1 to 4] versus 2 [range, 1 to 5]). The rate of complications, including neutropenic fever, emergency department visits, and hospitalizations, was higher after chemomobilization (30% versus 7.4%; P < .01). Previous use of ≤6 cycles of lenalidomide did not impair cell yield in either group. The median cost of mobilization was 17.4% lower in the G-CSF +/- PXF group (P = .01). Between group differences in time to engraftment were not clinically significant. Given similar rates of successful mobilization, similar engraftment time, and less toxicity and lower costs compared with chemomobilization, G-CSF with on-demand PXF may be preferable in myeloma patients with adequate disease control and limited lenalidomide exposure.
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http://dx.doi.org/10.1016/j.jtct.2021.04.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378276PMC
July 2021

Use of Backup Stem Cells for Stem Cell Boost and Second Transplant in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation.

Transplant Cell Ther 2021 05 25;27(5):405.e1-405.e6. Epub 2021 Feb 25.

Department of Medicine, Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, California.. Electronic address:

Autologous hematopoietic stem cell transplantation (ASCT) is a standard treatment for multiple myeloma (MM). Consensus guidelines recommend collecting sufficient stem cells in case there is a need for stem cell boost for delayed/poor engraftment or for future second ASCT. However, collecting and storing backup stem cells in all patients requires significant resources and cost, and the rates of backup stem cell utilization are not well studied. We sought to examine the utilization of backup stem cells (BSCs) in patients with MM undergoing ASCT. Patients with MM aged ≥18 years old who underwent first ASCT at our institution from January 2010 through December 2015 and collected sufficient stem cells for at least 2 transplants were included in this single-center retrospective study. This timeframe was selected to allow for adequate follow-up. A total of 393 patients were included. The median age was 58 years (range, 25-73). After a median follow-up of 6 years, the median progression-free survival (PFS) of the cohort was 3 years. Sixty-one percent (n = 240) of patients progressed or relapsed. Chemotherapy-based mobilization was used in almost all patients (98%). The median total CD34+ cells collected was 18.2 × 10/kg (range, 3.4-112.4). A median of 5.7 × 10 CD34+ cells/kg (range, 1.8-41.9) was infused during the first ASCT, and a median of 10.1 × 10 CD34+ cells/kg (range, 1.5-104.5) was cryopreserved for future use. Of the patients, 6.9% (n = 27) used backup stem cells, with 2.3% (n = 10) using them for stem cell boost, 4.6% (n = 18) for a second salvage ASCT, including 1 patient for both stem cell boost and second ASCT. Rates of backup stem cell use among patients aged <60, 60-69, and ≥70 years were 7.8%, 5.7%, and 5.9%, respectively. There was a trend toward higher rates of backup stem cell use for second ASCT in patients who were younger, had suboptimal disease control at time of first ASCT, and longer PFS. The median dose of stem cell boost given was 5.6 × 10 CD34+ cells/kg (range, 1.9-20). The median time from stem cell boost to neutrophil, hemoglobin, and platelet engraftment was 4 (range, 2-11), 15 (range, 4-34), and 12 (range, 0-34) days, respectively. Lower CD34+ dose and older age at time of ASCT predicted need for stem cell boost. With new salvage therapies for relapsed MM, the rates of second ASCT are very low. The low rates of use suggest that institutional policies regarding universal BSC collection and long-term storage should be reassessed and individualized. However, need for stem cell boost in 2.3% of patients may present a challenge to that.
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http://dx.doi.org/10.1016/j.jtct.2021.02.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113075PMC
May 2021

Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma.

Blood Adv 2021 01;5(1):143-155

Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA.

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed large B-cell lymphoma (LBCL). We evaluated the long-term course of hematologic recovery, immune reconstitution, and infectious complications in 41 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) at a single center. Grade 3+ cytopenias occurred in 97.6% of patients within the first 28 days postinfusion, with most resolved by 6 months. Overall, 63.4% of patients received a red blood cell transfusion, 34.1% of patients received a platelet transfusion, 36.6% of patients received IV immunoglobulin, and 51.2% of patients received growth factor (granulocyte colony-stimulating factor) injections beyond the first 28 days postinfusion. Only 40% of patients had recovered detectable CD19+ B cells by 1 year, and 50% of patients had a CD4+ T-cell count <200 cells per μL by 18 months postinfusion. Patients with durable responses to axi-cel had significantly longer durations of B-cell aplasia, and this duration correlated strongly with the recovery of CD4+ T-cell counts. There were significantly more infections within the first 28 days compared with any other period of follow-up, with the majority being mild-moderate in severity. Receipt of corticosteroids was the only factor that predicted risk of infection in a multivariate analysis (hazard ratio, 3.69; 95% confidence interval, 1.18-16.5). Opportunistic infections due to Pneumocystis jirovecii and varicella-zoster virus occurred up to 18 months postinfusion in patients who prematurely discontinued prophylaxis. These results support the use of comprehensive supportive care, including long-term monitoring and antimicrobial prophylaxis, beyond 12 months after axi-cel treatment.
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http://dx.doi.org/10.1182/bloodadvances.2020002732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805341PMC
January 2021

CD22-directed CAR T-cell therapy induces complete remissions in CD19-directed CAR-refractory large B-cell lymphoma.

Blood 2021 Apr;137(17):2321-2325

Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA.

The prognosis of patients with large B-cell lymphoma (LBCL) that progresses after treatment with chimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CAR19) is poor. We report on the first 3 consecutive patients with autologous CAR19-refractory LBCL who were treated with a single infusion of autologous 1 × 106 CAR+ T cells per kilogram targeting CD22 (CAR22) as part of a phase 1 dose-escalation study. CAR22 therapy was relatively well tolerated, without any observed nonhematologic adverse events higher than grade 2. After infusion, all 3 patients achieved complete remission, with all responses continuing at the time of last follow-up (mean, 7.8 months; range, 6-9.3). Circulating CAR22 cells demonstrated robust expansion (peak range, 85.4-350 cells per microliter), and persisted beyond 3 months in all patients with continued radiographic responses and corresponding decreases in circulating tumor DNA beyond 6 months after infusion. Further accrual at a higher dose level in this phase 1 dose-escalation study is ongoing and will explore the role of this therapy in patients in whom prior CAR T-cell therapies have failed. This trial is registered on clinicaltrials.gov as #NCT04088890.
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http://dx.doi.org/10.1182/blood.2020009432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085484PMC
April 2021

Transgender and Intersex Athletes in Single-sex Sports.

Authors:
Laura Johnston

J Law Med 2020 Dec;28(1):197-213

Medical and Integrity Policy Coordinator, Rugby Australia.

Transgender and intersex athlete inclusion and exclusion from single-sex sports is an area of ongoing conversation and change. This article discusses the separation of male and female athletes, looking at the scientific reasoning, the Australian legislation, Australian case law and sport-specific policies. The role of sports' policies and case examples for transgender and intersex athletes are investigated along with the concepts of discrimination and legality. The article concludes that policies and regulations can be discriminatory while still being lawful if they meet relevant exceptions - as outlined by legislation and set out by courts. More research is required in the area of the potential advantage that transgender and intersex athletes may have in both individual and team single-sex sports before definitive statements regarding inclusion or exclusion can be made.
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December 2020

Oral conditions in the community patient: part 2-systemic complications of poor oral health.

Br J Community Nurs 2020 Nov;25(11):532-536

Academic Dental Core Trainee, Birmingham Dental Hospital and School of Dentistry, Edgbaston.

Oral health has a symbiotic relationship with general health, with oral disease recognised to have an adverse effect on the overall systemic health of a patient. Deterioration in oral health has been shown to have an impact on the severity of chronic systemic diseases, nutrition, hydration and psychological and social wellbeing. Part 1 of this mini-series explored the common oral conditions that community patients may present with, and the role of the nursing team in aiding the prevention, diagnosis and management of these conditions. Following on from that, this article discusses the links between oral and general health, and preservation of a patient's quality of life. This article also aims to support nurses' knowledge on how to assess the oral health needs of patients, support oral care provision, how to access acute and elective dental services and signpost to additional supportive resources.
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http://dx.doi.org/10.12968/bjcn.2020.25.11.532DOI Listing
November 2020

Widely Used Mutants of , Encoding the Tumor Necrosis Factor, Carry Additional Mutations in the NimrodC1 Phagocytosis Receptor.

G3 (Bethesda) 2020 12 3;10(12):4707-4712. Epub 2020 Dec 3.

Department of Genetics & Development, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, New York, NY

The process of apoptosis in epithelia involves activation of caspases, delamination of cells, and degradation of cellular components. Corpses and cellular debris are then rapidly cleared from the tissue by phagocytic blood cells. In studies of the TNF, Eiger (Egr) and cell death in wing imaginal discs, the epithelial primordia of fly wings, we noticed that dying cells appeared to transiently accumulate in mutant wing discs, raising the possibility that their phagocytic engulfment by hemocytes was impaired. Further investigation revealed that lymph glands and circulating hemocytes from mutant larvae were completely devoid of NimC1 staining, a marker of phagocytic hemocytes. Genome sequencing uncovered mutations in the coding region that are predicted to truncate the NimC1 protein before its transmembrane domain, and provide an explanation for the lack of NimC staining. The work that we report here demonstrates the presence of these mutations in the widely used mutant, its sister allele, , and its parental strain, As the and alleles have been used in numerous studies of immunity and cell death, it may be advisable to re-evaluate their associated phenotypes.
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http://dx.doi.org/10.1534/g3.120.401800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718733PMC
December 2020

Oral conditions in the community patient: part 1.

Br J Community Nurs 2020 Oct;25(10):490-495

Speciality Registrar in Paediatric Dentistry, Birmingham Dental Hospital and School of Dentistry, Edgbaston.

Oral health is essential to prevent pain, ensure adequate nutrition and promote optimum general and psychosocial wellbeing. The detrimental effects of poor oral health can often be overlooked, resulting in low prioritisation of oral care when compared to other care roles. A multidisciplinary approach to maintaining good oral health of dependent community patients must be established, with stakeholders including dentists, nurses, carers, and family members. This article aims to explore fundamental oral health considerations for community nurses to maintain oral health.
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http://dx.doi.org/10.12968/bjcn.2020.25.10.490DOI Listing
October 2020

Outcomes with Autologous or Allogeneic Stem Cell Transplantation in Patients with Plasma Cell Leukemia in the Era of Novel Agents.

Biol Blood Marrow Transplant 2020 12 19;26(12):e328-e332. Epub 2020 Sep 19.

Stanford Cancer Institute, Stanford University Medical Center, Stanford, California. Electronic address:

Plasma cell leukemia (PCL) is a rare and very aggressive plasma cell disorder. The optimal treatment approach, including whether to pursue an autologous (auto) or allogeneic (allo) stem cell transplantation (SCT) is not clear, given the lack of clinical trial-based evidence. This single-center retrospective study describes the outcomes of 16 patients with PCL (n = 14 with primary PCL) who underwent either autoSCT (n = 9) or alloSCT (n = 7) for PCL in the era of novel agents, between 2007 and 2019. The median age of the cohort was 58 years. High-risk cytogenetics were found in 50% of the patients. All patients received a proteasome inhibitor and/or immunomodulatory drug-based regimen before transplantation. At the time of transplantation, 10 patients (62%) obtained at least a very good partial response (VGPR). The response after autoSCT (3 months) was at least a VGPR in 6 patients (67%; complete response [CR] in 5). All patients undergoing alloSCT achieved a CR at 3 months. Maintenance therapy was provided to 5 patients (56%) after autoSCT. The median progression-free survival after transplantation was 6 months in the autoSCT group, compared with 18 months in the alloSCT group (P = .09), and median overall survival (OS) after transplantation in the 2 groups was 19 months and 40 months, respectively (P = .41). The median OS from diagnosis was 27 months and 49 months, respectively (P = .50). Of the 11 deaths, 10 patients (91%) died of relapsed disease. AlloSCT was not observed to offer any significant survival advantage over autoSCT in PCL, in agreement with recent reports, and relapse remains the primary cause of death in these patients.
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http://dx.doi.org/10.1016/j.bbmt.2020.08.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083942PMC
December 2020

Nonmyeloablative allogeneic transplantation achieves clinical and molecular remission in cutaneous T-cell lymphoma.

Blood Adv 2020 09;4(18):4474-4482

Department of Dermatology.

The majority of patients with refractory, advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS) have a life expectancy of <5 years. Here, we report a phase 2 study of a novel nonmyeloablative allogeneic transplantation strategy tailored for this patient population. This study has completed the enrollment, and 35 patients (13 MF, 22 SS) have undergone transplant as planned. The majority (80%) of the patients had stage IV disease and received multiple previous systemic therapies. All patients had active disease at the time of conditioning using total skin electron beam therapy, total lymphoid irradiation, and antithymocyte globulin, and received allograft infusion as outpatients. Cyclosporine or tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. Patients tolerated the transplant well, with 1- and 2-year nonrelapse mortality of 3% and 14%, respectively. The day +180 cumulative incidence of grade 2 to 4 acute GVHD was 16%, and the 2-year incidence of moderate/severe chronic GVHD was 32%. With a median posttransplant follow-up of 5.4 years, the 2-, 3-, and 5-year overall survival rates were 68%, 62%, and 56%. Using high-throughput sequencing of the T-cell receptor for minimal residual disease monitoring, we observed that 43% achieved molecular remission, which was associated with a lower incidence of disease progression or relapse (9% vs 87%; P = .02). Our study also showed that patients who were aged ≥65 years at the time of allotransplant had similar clinical outcomes compared with younger patients. Thus, we have developed an alternative and potentially curative nonmyeloablative allogeneic transplant regimen for patients with advanced stage MF/SS. This trial was registered at www.clinicaltrials.gov as #NCT00896493.
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http://dx.doi.org/10.1182/bloodadvances.2020001627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509879PMC
September 2020

Outcomes with autologous stem cell transplant vs. non-transplant therapy in patients 70 years and older with multiple myeloma.

Bone Marrow Transplant 2021 02 11;56(2):368-375. Epub 2020 Aug 11.

Stanford Cancer Institute, Stanford University Medical Center, Stanford, CA, USA.

We evaluated 79 patients with multiple myeloma (MM) ≥70 years referred to our blood and marrow transplant clinic, within 1 year of diagnosis from 2010 to 2019, for consideration of autologous stem cell transplant (ASCT). Thirty-eight (48%) of 79 patients underwent ASCT. ASCT was not pursued in 41 (52%) patients due to: patient or physician preference in 80% (n = 33) or ineligibility in 20% (n = 8). Baseline characteristics of patients in the two groups were similar. Median PFS from treatment start amongst patients undergoing ASCT (n = 38) vs. not (n = 41) was 41 months vs. 33 months, p = 0.03. There was no difference in OS, with estimated 5-year OS of 73% vs. 83%, respectively (p = 0.86). Day +100 transplant-related mortality (TRM) was 0%. ASCT was an independent favorable prognostic factor for PFS in multivariate analysis, after accounting for HCT-CI score, performance status, hematologic response, and maintenance. Finally, patients ≥70 years undergoing ASCT had similar PFS compared to a contemporaneous institutional cohort of patients <70 years (n = 631) (median PFS from transplant: 36 vs. 47 months, p = 0.25). In this retrospective analysis, ASCT was associated with low TRM and better PFS in fit older adults with MM compared to non-transplant therapy, with comparable benefits as seen in younger patients.
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http://dx.doi.org/10.1038/s41409-020-01026-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019397PMC
February 2021

Swapping drills for dressings: redeployment of dentists to community nursing.

Br J Community Nurs 2020 Jun;25(6):266-270

Speciality Registrar in Oral Surgery, at Birmingham Dental Hospital and School of Dentistry, Edgbaston.

The COVID-19 pandemic has placed increased strain on many aspects of the NHS. Dentists have been identified as having skills transferable to support community nursing teams as part of the redeployment response. This article aims to explore the roles dentists have undertaken within the community setting and reflect on dentists' transferable skills, training and personal experiences during redeployment. Despite differences in healthcare delivery, both professions share skills surrounding professionalism, communication, raising concerns and consent. Community nurses have supported dentists through specific training and competencies so that the latter are equipped with skills to support roles including wound care, catheter care and medication administration. Dentists have been well-received by community nursing colleagues and patients during redeployment. This experience has enabled redeployed dentists to establish new skillsets while improving their appreciation for the fundamental role that community nurses play within society.
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http://dx.doi.org/10.12968/bjcn.2020.25.6.266DOI Listing
June 2020

Machine Learning Algorithms to Differentiate Among Pulmonary Complications After Hematopoietic Cell Transplant.

Chest 2020 09 25;158(3):1090-1103. Epub 2020 Apr 25.

Department of Medicine, the Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University School of Medicine, Stanford, CA. Electronic address:

Background: Pulmonary complications, including infections, are highly prevalent in patients after hematopoietic cell transplantation with chronic graft-vs-host disease. These comorbid diseases can make the diagnosis of early lung graft-vs-host disease (bronchiolitis obliterans syndrome) challenging. A quantitative method to differentiate among these pulmonary diseases can address diagnostic challenges and facilitate earlier and more targeted therapy.

Study Design And Methods: We conducted a single-center study of 66 patients with CT chest scans analyzed with a quantitative imaging tool known as parametric response mapping. Parametric response mapping results were correlated with pulmonary function tests and clinical characteristics. Five parametric response mapping metrics were applied to K-means clustering and support vector machine models to distinguish among posttransplantation lung complications solely from quantitative output.

Results: Compared with parametric response mapping, spirometry showed a moderate correlation with radiographic air trapping, and total lung capacity and residual volume showed a strong correlation with radiographic lung volumes. K-means clustering analysis distinguished four unique clusters. Clusters 2 and 3 represented obstructive physiology (encompassing 81% of patients with bronchiolitis obliterans syndrome) in increasing severity (percentage air trapping 15.6% and 43.0%, respectively). Cluster 1 was dominated by normal lung, and cluster 4 was characterized by patients with parenchymal opacities. A support vector machine algorithm differentiated bronchiolitis obliterans syndrome with a specificity of 88%, sensitivity of 83%, accuracy of 86%, and an area under the receiver operating characteristic curve of 0.85.

Interpretation: Our machine learning models offer a quantitative approach for the identification of bronchiolitis obliterans syndrome vs other lung diseases, including late pulmonary complications after hematopoietic cell transplantation.
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http://dx.doi.org/10.1016/j.chest.2020.02.076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097633PMC
September 2020

Functional Impact of Human Genetic Variants of /Endostatin on Pulmonary Endothelium.

Am J Respir Cell Mol Biol 2020 04;62(4):524-534

Division of Pulmonary and Critical Care Medicine, Department of Medicine, and.

Pulmonary arterial hypertension (PAH) is an incurable disease characterized by disordered and dysfunctional angiogenesis leading to small-vessel loss and an obliterative vasculopathy. The pathogenesis of PAH is not fully understood, but multiple studies have demonstrated links between elevated angiostatic factors, disease severity, and adverse clinical outcomes. ES (endostatin), one such circulating angiostatic peptide, is the cleavage product of the proteoglycan (collagen α1[XVIII] chain). Elevated serum ES is associated with increased mortality and disease severity in PAH. A nonsynonymous variant of ES (aspartic acid-to-asparagine substitution at amino acid 104; p.D104N) is associated with differences in PAH survival. Although /ES expression is markedly increased in remodeled pulmonary vessels in PAH, the impact of ES on pulmonary endothelial cell (PEC) biology and molecular contributions to PAH severity remain undetermined. In the present study, we characterized the effects of exogenous ES on human PEC biology and signaling. We demonstrated that ES inhibits PEC migration, proliferation, and cell survival, with significant differences between human variants, indicating that they are functional genetic variants. ES promotes proteasome-mediated degradation of the transcriptional repressor ID1, increasing expression and release of TSP-1 (thrombospondin 1). ES inhibits PEC migration via an ID1/TSP-1/CD36-dependent pathway, in contrast to proliferation and apoptosis, which require both CD36 and CD47. Collectively, the data implicate ES as a novel negative regulator of ID1 and an upstream propagator of an angiostatic signal cascade converging on CD36 and CD47, providing insight into the cellular and molecular effects of a functional genetic variant linked to altered outcomes in PAH.
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http://dx.doi.org/10.1165/rcmb.2019-0056OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110972PMC
April 2020

Hematopoietic Cell Transplantation in the Treatment of Adult Acute Lymphoblastic Leukemia: Updated 2019 Evidence-Based Review from the American Society for Transplantation and Cellular Therapy.

Biol Blood Marrow Transplant 2019 11 22;25(11):2113-2123. Epub 2019 Aug 22.

Division of Hematology/Oncology/Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, MN.

The role of hematopoietic cell transplantation (HCT) in adults with acute lymphoblastic leukemia (ALL) is reviewed and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of ALL experts developed consensus on the treatment recommendations based on the evidence. Allogeneic HCT offers a survival benefit in selected patients with ALL, and this review summarizes the standard indications as well as the areas of controversy. There is now greater experience with pediatric-inspired chemotherapy regimens that has transformed upfront therapy for adult ALL, resulting in higher remission rates and overall survival. This in turn has increased the equipoise around decision making for ALL in first complete remission (CR1) when there is no measurable residual disease (MRD) at the end of induction and/or consolidation. Randomized studies are needed for adults with ALL to compare allogeneic HCT in CR1 with pediatric-inspired chemotherapy alone. Indications for transplantation in the evolving landscape of MRD assessments and novel targeted and immune therapeutics remain important areas of investigation.
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http://dx.doi.org/10.1016/j.bbmt.2019.08.014DOI Listing
November 2019

Nonmyeloablative TLI-ATG conditioning for allogeneic transplantation: mature follow-up from a large single-center cohort.

Blood Adv 2019 08;3(16):2454-2464

Division of Blood and Marrow Transplantation, Department of Medicine.

Nonmyeloablative total lymphoid irradiation and antithymocyte globulin (TLI-ATG) conditioning is protective against graft-versus-host disease (GVHD), while retaining graft-versus-tumor activity across various hematologic malignancies. We report our comprehensive experience using TLI-ATG conditioning in 612 patients with hematologic malignancies who underwent allogeneic transplantation at Stanford University from 2001 to 2016. All patients received granulocyte colony-stimulating factor-mobilized peripheral blood grafts and cyclosporine and mycophenolate mofetil for GVHD prophylaxis. The median age was 60 years (range, 21-78), with a median follow-up of 6.0 years (range, 1.0-16.4). Common diagnoses included acute myeloid leukemia (AML; n = 193), myelodysplastic syndrome (MDS; n = 94), chronic lymphocytic leukemia (CLL; n = 80), non-Hodgkin lymphoma (NHL; n = 175), and Hodgkin lymphoma (HL; n = 35). Thirty-four percent of patients had a comorbidity index ≥3, 30% had a high to very high disease risk index, and 56% received unrelated donor grafts, including 15% with HLA-mismatched donors. Ninety-eight percent underwent transplant in the outpatient setting, and 57% were never hospitalized from days 0 through 100. The 1-year rates of nonrelapse mortality (NRM), grade II-IV acute GVHD, and extensive chronic GVHD were 9%, 14%, and 22%, respectively. The 4-year estimates for overall and progression-free survival were 42% and 32% for AML, 30% and 21% for MDS, 67% and 43% for CLL, 68% and 45% for NHL, and 78% and 49% for HL. Mixed chimerism correlated with the risk of relapse. TLI-ATG conditioning was well tolerated, with low rates of GVHD and NRM. Durable remissions were observed across hematologic malignancies, with particularly favorable outcomes for heavily pretreated lymphomas. Several efforts are underway to augment donor chimerism and reduce relapse rates while maintaining the favorable safety and tolerability profile of this regimen.
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http://dx.doi.org/10.1182/bloodadvances.2019000297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712526PMC
August 2019

Psychiatric Assistance Dog Use for People Living With Mental Health Disorders.

Front Vet Sci 2019 6;6:166. Epub 2019 Jun 6.

Independent Researcher, Sydney, NSW, Australia.

A psychiatric assistance dog (PAD) is a service dog that is trained to assist its handler (owner) who has been diagnosed with a mental health condition such as post-traumatic stress disorder (PTSD), schizophrenia, depression, anxiety, or bipolar disorder. Literature searches reveal that little is known about the population of people who own PADs, the types of dogs used or the functions they provide. One third ( = 199) of PAD owners in Australia registered with the charity "mindDog" participated in an online survey designed to better understand the person and dog team. Participants learned about PADs through the internet (37%), health care practitioners (32%), or family/friends (30%). The dogs in the sample were of varying age, gender and breed. The most common reasons for people to choose a dog to be a PAD were temperament (60%) and size/weight (48%). Just under half (48%) of the dogs had been acquired by the owner specifically to be trained as a PAD, and the rest were existing pets. All the dogs were trained by the owner or a combination of the owner and a qualified trainer; none were trained exclusively by assistance/service dog provider organizations. The median age of the participants at the time of data collection was 47 years, ranging from 10 to 75 years. Most (77%) identified as female. Depression (84%), anxiety (social 61%; generalized 60%), PTSD (62%), and panic attacks (57%) were the most reported mental health diagnoses. Tasks the dogs performed for their owners included: reduction of anxiety through tactile stimulation (94%); nudging/pawing to bring back to the present (71%); interrupting undesirable behavior (51%); constant body contact (50%); deep pressure stimulation (45%) and blocking contact from other people (42%). PAD usage decreased (46%), increased (30%) or did not change (24%) participants' use of psychiatric or other health care services. Decrease in service use was mainly due to reduced suicide attempts, and less requirement for hospitalization and medication; increased use was mainly due to enhanced ability to attend appointments. Results of this study show that PAD owners have differing mental health diagnoses, and their dogs perform different tasks to support them in daily life. Every participant described the relationship with his/her PAD as positive, suggesting that a successful working partnership does not require the dog to have been bred or raised specifically for the role. A better understanding of this population and the person-dog relationship will inform the appropriate choice, training and use of PADs for people living with mental health problems.
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http://dx.doi.org/10.3389/fvets.2019.00166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563823PMC
June 2019

SU5416 does not attenuate early RV angiogenesis in the murine chronic hypoxia PH model.

Respir Res 2019 Jun 17;20(1):123. Epub 2019 Jun 17.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, 1830 E. Monument Street, 5th Floor, Baltimore, MD, 21205, USA.

Background: Right ventricular (RV) angiogenesis has been associated with adaptive myocardial remodeling in pulmonary hypertension (PH), though molecular regulators are poorly defined. Endothelial cell VEGFR-2 is considered a "master regulator" of angiogenesis in other models, and the small molecule VEGF receptor tyrosine kinase inhibitor SU5416 is commonly used to generate PH in rodents. We hypothesized that SU5416, through direct effects on cardiac endothelial cell VEGFR-2, would attenuate RV angiogenesis in a murine model of PH.

Methods: C57 BL/6 mice were exposed to chronic hypoxia (CH-PH) to generate PH and stimulate RV angiogenesis. SU5416 (20 mg/kg) or vehicle were administered at the start of the CH exposure, and weekly thereafter. Angiogenesis was measured after one week of CH-PH using a combination of unbiased stereological measurements and flow cytometry-based quantification of myocardial endothelial cell proliferation. In complementary experiments, primary cardiac endothelial cells from C57 BL/6 mice were exposed to recombinant VEGF (50 ng/mL) or grown on Matrigel in the presence of SU5416 (5 μM) or vehicle.

Result: SU5416 directly inhibited VEGF-mediated ERK phosphorylation, cell proliferation, and Kdr transcription, but not Matrigel tube formation in primary murine cardiac endothelial cells in vitro. SU5416 did not inhibit CH-PH induced RV angiogenesis, endothelial cell proliferation, or RV hypertrophy in vivo, despite significantly altering the expression profile of genes involved in angiogenesis.

Conclusions: These findings demonstrate that SU5416 directly inhibited VEGF-induced proliferation of murine cardiac endothelial cells but does not attenuate CH-PH induced RV angiogenesis or myocardial remodeling in vivo.
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http://dx.doi.org/10.1186/s12931-019-1079-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580559PMC
June 2019

Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)-an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT).

Bone Marrow Transplant 2019 11 15;54(11):1868-1880. Epub 2019 May 15.

Department of Haematological Medicine, King's College, London, UK.

On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor-T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring and disease assessments. To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.
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http://dx.doi.org/10.1038/s41409-019-0451-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268756PMC
November 2019
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