Purpose: Anti-CD19 chimeric antigen receptor T-cell immunotherapy (19CAR-T) has achieved impressive clinical results in adult and pediatric relapsed/refractory (r/r) B-lineage acute lymphoblastic leukemia (B-ALL). However, the application and effect of CAR-T therapy in B-ALL patients with extramedullary relapse are rarely issued even disqualified in some clinical trials. Here, we examined the efficacy of 19CAR-T in patients with both bone marrow and extramedullary involvement.
Materials And Methods: CAR-T cells were generated by transfection of primary human T lymphocytes with a lentiviral vector expressing anti-CD19 single chain antibody fragments (scFvs) with the cytoplasmic domains of 4-1BB and CD3ζ, and used to infuse patients diagnosed as having r/r B-ALL with extramedullary origination. Clinical responses were evaluated by the use of bone marrow aspiration, imaging, and flow cytometry.
Results: Eight patients received 19CAR-T infusion and all attained complete remission (CR). Only one patient was bridged to hematopoietic stem cell transplantation (HSCT). Although three patients relapsed after infusion, they received 19/22CAR-T infusion sequentially and attained a second remission. To date, five patients are in continuous CR and all eight patients are still alive. The mean follow-up time was 21.9 months, while the 24-month estimated event-free survival is 51.4%.
Conclusion: 19CAR-T therapy can lead to clinical remission for extramedullary relapsed pediatric B-ALL patients. However, the problem of CD19+ relapses after CAR-T remained to be solved. For patients relapsing after CAR-T, a second CAR-T therapy creates another opportunity for remission for subsequent HSCT.
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http://dx.doi.org/10.4143/crt.2021.399 | DOI Listing |
Clin Cancer Res
January 2025
Bristol-Myers Squibb (United States), Summit, New Jersey, United States.
Purpose: Orvacabtagene autoleucel (orva-cel; JCARH125), a CAR T-cell therapy targeting B-cell maturation antigen (BCMA), was evaluated in relapsed/refractory multiple myeloma (RRMM) patients in the EVOLVE phase 1/2 study (NCT03430011). We applied a modified piecewise model to characterize orva-cel transgene kinetics and assessed the impact of various covariates on its pharmacokinetics (PK).
Experimental Design: The population PK analysis included 159 patients from the EVOLVE study.
Stem Cell Rev Rep
January 2025
Institute for Cellular and Molecular Medicine, Department of Immunology, SAMRC Extramural Unit for Stem Cell Research and Therapy, University of Pretoria, Pretoria, 0084, South Africa.
Histochem Cell Biol
January 2025
Department of Histology and Embryology, Faculty of Medicine, Ankara Yildirim Beyazit University, 06800, Ankara, Turkey.
Bone marrow mesenchymal stromal cells (BM-MSCs) are integral components of the bone marrow microenvironment, playing a crucial role in supporting hematopoiesis. Recent studies have investigated the potential involvement of BM-MSCs in the pathophysiology of acute lymphoblastic leukemia (ALL). However, the exact contribution of BM-MSCs to leukemia progression remains unclear because of conflicting findings and limited characterization.
View Article and Find Full Text PDFRadiologie (Heidelb)
January 2025
Department of Radiology, The Affiliated Hospital of Wuhan Sports University, 430079, Wuhan, China.
Objective: This study aimed to explore and evaluate a novel method for diagnosing patellar chondromalacia using radiomic features from patellar sagittal T2-weighted images (T2WI).
Methods: The experimental data included sagittal T2WI images of the patella from 40 patients with patellar chondromalacia and 40 healthy volunteers. The training set comprised 30 cases of chondromalacia and 30 healthy volunteers, while the test set included 10 cases of each.
ACS Appl Mater Interfaces
January 2025
Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States.
The innate immune system is tightly regulated by a complex network of chemical signals triggered by pathogens, cellular damage, and environmental stimuli. While it is well-established that changes in the extracellular environment can significantly influence the immune response to pathogens and damage-associated molecules, there remains a limited understanding of how changes in environmental stimuli specifically impact the activation of the NLRP3 inflammasome, a key component of innate immunity. Here, we demonstrated how shear stress can act as Signal 2 in the NLRP3 inflammasome activation pathway by treating LPS-primed immortalized bone marrow-derived macrophages (iBMDMs) with several physiologically relevant magnitudes of shear stress to induce inflammasome activation.
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