scholarly journals Newly developed pseudogout arthritis after therapy with MAGE-A4 directed TCR T cells responded to treatment with tocilizumab

2021 ◽  
Vol 9 (7) ◽  
pp. e002716
Author(s):  
Sang T. Kim ◽  
Jean Tayar ◽  
Siqing Fu ◽  
Danxia Ke ◽  
Elliot Norry ◽  
...  
Keyword(s):  
T Cells ◽  
Synovial Fluid ◽  
Th17 Cells ◽  
Effector Cell ◽  
Calcium Pyrophosphate ◽  
Calcium Pyrophosphate Dihydrate ◽  
Immune Effector Cell ◽  
Cell Therapies ◽  
Immune Effector ◽  
Pyrophosphate Dihydrate

With durable cancer responses, genetically modified cell therapies are being implemented in various cancers. However, these immune effector cell therapies can cause toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Pseudogout arthritis is an inflammatory arthritis induced by deposition of calcium pyrophosphate dihydrate crystals. Here, we report a case of pseudogout arthritis in a patient treated with MAGE-A4 directed T cell receptor T cells, for fallopian tube cancer. The patient developed CRS and ICANS 7 days after infusion of the T cells. Concurrently, the patient newly developed sudden onset of left knee arthritis. Synovial fluid analyses revealed the presence of calcium pyrophosphate dihydrate crystal. Notably, the pseudogout arthritis was resolved with tocilizumab, which was administered for the treatment of CRS and ICANS. Immunoprofiling of the synovial fluid showed that the proportion of inflammatory interleukin 17 (IL-17)-producing CD4+ T (Th17) cells and amount of IL-6 were notably increased, suggesting a potential role of Th17 cells in pseudogout arthritis after T-cell therapy. To the best of our knowledge, this is the first reported case of pseudogout arthritis after cell therapy. Clinicians, especially hematologists, oncologists and rheumatologists, should be aware that pseudogout arthritis can be associated with CRS/ICANS.

scholarly journals Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events

2020 ◽  
Vol 8 (2) ◽  
pp. e001511
Author(s):  
Marcela V Maus ◽  
Sara Alexander ◽  
Michael R Bishop ◽  
Jennifer N Brudno ◽  
Colleen Callahan ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Clinical Practice Guideline ◽  
Practice Guideline ◽  
Effector Cell ◽  
Cancer Therapeutics ◽  
Immune Effector Cell ◽  
Cell Therapies ◽  
Immune Effector ◽  
Hematological Cancers ◽  
Immunotherapy Of Cancer

Immune effector cell (IEC) therapies offer durable and sustained remissions in significant numbers of patients with hematological cancers. While these unique immunotherapies have improved outcomes for pediatric and adult patients in a number of disease states, as ‘living drugs,’ their toxicity profiles, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), differ markedly from conventional cancer therapeutics. At the time of article preparation, the US Food and Drug Administration (FDA) has approved tisagenlecleucel, axicabtagene ciloleucel, and brexucabtagene autoleucel, all of which are IEC therapies based on genetically modified T cells engineered to express chimeric antigen receptors (CARs), and additional products are expected to reach marketing authorization soon and to enter clinical development in due course. As IEC therapies, especially CAR T cell therapies, enter more widespread clinical use, there is a need for clear, cohesive recommendations on toxicity management, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of common toxicities in the context of IEC treatment, including baseline laboratory parameters for monitoring, timing to onset, and pharmacological interventions, ultimately forming evidence- and consensus-based recommendations to assist medical professionals in decision-making and to improve outcomes for patients.

scholarly journals Practical aspects of building a new immunotherapy program: the future of cell therapy

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 579-584
Author(s):  
Jesús G. Berdeja
Keyword(s):  
T Cells ◽  
Effector Cell ◽  
Hematologic Malignancies ◽  
Immune Effector Cell ◽  
Optimal Care ◽  
Immune Effector ◽  
Car T Cells ◽  
Car T ◽  
Challenges And Opportunities ◽  
Disease Specialist

Abstract Cellular-redirecting therapies, including bispecific T-cell engagers and chimeric antigen receptor (CAR) T cells, are rapidly changing the treatment landscape of hematologic malignancies and solid tumor malignancies. I will discuss the unique safety profile and logistical aspects that pose challenges and opportunities for the safe and successful delivery of these therapies. Close interaction, communication, and established partnerships between the primary oncologist, the disease specialist, and the immune effector cell provider will be needed to provide optimal care longitudinally for any patient. I will discuss practical ways for any program to deliver these therapies and how future advances may widen availability beyond just a few centers.

scholarly journals Accuracy of synovial fluid analysis compared to histology for the identification of calcium pyrophosphate crystals: an ancillary study of the OMERACT US Working Group - CPPD subgroup

Reumatismo ◽  
2021 ◽  
Vol 73 (2) ◽  
pp. 106-110
Author(s):  
S. Sirotti ◽  
M. Gutierrez ◽  
C. Pineda ◽  
D. Clavijo-Cornejo ◽  
T. Serban ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Light Microscopy ◽  
Microscopic Analysis ◽  
Calcium Pyrophosphate ◽  
Calcium Pyrophosphate Dihydrate ◽  
Ancillary Study ◽  
Fluid Analysis ◽  
Synovial Fluid Analysis ◽  
Pyrophosphate Dihydrate ◽  
Calcium Pyrophosphate Dihydrate Crystals

The aim of this study was to evaluate the accuracy of synovial fluid analysis in the identification of calcium pyrophosphate dihydrate crystals compared to microscopic analysis of joint tissues as the reference standard. This is an ancillary study of an international, multicentre cross-sectional study performed by the calcium pyrophosphate deposition disease (CPPD) subgroup of the OMERACT Ultrasound working group. Consecutive patients with knee osteoarthritis (OA) waiting for total knee replacement surgery were enrolled in the study from 2 participating centres in Mexico and Romania. During the surgical procedures, synovial fluid, menisci and hyaline cartilage were collected and analysed within 48 hours from surgery under transmitted light microscopy and compensated polarised light microscopy for the presence/absence of calcium pyrophosphate crystals. All slides were analysed by expert examiners on site, blinded to other findings. A dichotomic score (absence/ presence) was used for scoring both synovial fluid and tissues. Microscopic analysis of knee tissues was considered the gold standard. Sensitivity, specificity, accuracy, positive and negative predictive values of synovial fluid analysis in the identification of calcium pyrophosphate crystals were calculated. 15 patients (53% female, mean age 68 yo ± 8.4) with OA of grade 3 or 4 according to Kellgren-Lawrence scoring were enrolled. 12 patients (80%) were positive for calcium pyrophosphate crystals at the synovial fluid analysis and 14 (93%) at the tissue microscopic analysis. The overall diagnostic accuracy of synovial fluid analysis compared with histology for CPPD was 87%, with a sensitivity of 86% and a specificity of 100%, the positive predictive value was 100% and the negative predictive value was 33%. In conclusion synovial fluid analysis proved to be an accurate test for the identification of calcium pyrophosphate dihydrate crystals in patients with advanced OA.

scholarly journals DIFFERENTIAL MEMBRANOLYTIC EFFECTS OF MICROCRYSTALLINE SODIUM URATE AND CALCIUM PYROPHOSPHATE DIHYDRATE

1971 ◽  
Vol 133 (1) ◽  
pp. 100-112 ◽  
Author(s):  
Walter R. Wallingford ◽  
Daniel J. McCarty
Keyword(s):  
Synovial Fluid ◽  
Time Course ◽  
Calcium Pyrophosphate ◽  
Erythrocyte Membranes ◽  
Calcium Pyrophosphate Dihydrate ◽  
Hydrogen Acceptor ◽  
Erythrocyte Hemolysis ◽  
Reaction Curve ◽  
Pyrophosphate Dihydrate ◽  
Sodium Urate

Microcrystals of sodium urate produced direct lysis of erythrocyte membranes, as had been described previously for silica. Calcium pyrophosphate crystals induced modest erythrocyte hemolysis, also, and time-course experiments showed a markedly different reaction curve from those produced by silica and urate. Polyvinylpyridine-N-oxide, a strong hydrogen acceptor, was bound from solution to urate and silica, but not to calcium pyrophosphate crystals; this compound effectively blocked urate and silica, but not calcium pyrophosphate or control hemolysis. Dextran and heparin inhibited urate-but not silica-induced hemolysis. If erythrocyte and lysosome membranes react similarly to these particles, then the absence of phagosomes in gouty synovial fluid leukocytes, and the presence of these structures in pseudogout, may be explained.

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