4 research outputs found
Giant mycotic right coronary aneurism: A rare complication of Staphylococcus aureus native valve endocarditis
International audienc
Evaluation of a new ELISA assay for monoclonal freeâlight chain detection in patients with cardiac amyloidosis
Abstract The causal protein of amyloid lightâchain (AL) amyloidosis is a monoclonal immunoglobulin free light chain (mFLC), which must be quantified in the serum for patient diagnosis and monitoring. Several manufacturers commercialize immunoassays that quantify total kappa (Îș) and lambda (λ) FLC, but results can differ greatly between these tests. Here, we compared a recently developed enzymeâlinked immunosorbent assay (ELISA) (Sebia) with NâLatex immunonephelometry (Siemens) in 96 patients diagnosed with AL amyloidosis (histologically confirmed) and 48 nonâAL patients sent to our referral center for suspicion of cardiac amyloidosis. ELISA freeâlight chain difference (dFLC) were lower than NâLatex values, and agreement between methods was reduced in the case of involved λ FLC. Diagnosis sensitivity and specificity were >85% with both assays. A receiver operating characteristic analysis indicated that ELISA performances could be improved by using a higher value for the lower limit of the Îș/λ ratio. We also assessed Freelite (The Binding Site) in a subgroup of these same AL patients, including 18 cases with normal Îș/λ ratio by at least one assay. Only two patients had normal Îș/λ ratio with all three assays. Overall, ELISA demonstrated slightly lower sensitivity than NâLatex but may be an alternative to nephelometry/turbidimetry in certain difficult cases
HLA-DR expression on monocytes and outcome of anti-CD19 CAR T-cell therapy for large B-cell lymphoma
Abstract Despite their unprecedented success in relapsed/refractory (R/R) large B-cell lymphoma (LBCL), anti-CD19 CAR T cells are associated with significant toxicity, and more than half of patients relapse. As monocytes emerged as key players in CAR therapy, we sought to evaluate the evolution of HLA-DR expression on monocytes (mHLA-DR) before and after commercial anti-CD19 CAR T-cell infusion in a large cohort (n = 103) of patients with R/R LBCL and its association with adverse events and treatment response. Cy-Flu-based lymphodepletion (LD) upregulated mHLA-DR in 79% of the cases, whereas in 2l% of cases (15 patients), the mHLA-DR level decreased after LD, and this decrease was associated with poorer outcome. Low mHLA-DR at day minus 7 (Dâ7) (<13â500 antibodies per cell) before CAR T-cell infusion correlated with older age, poorer performance status, higher tumor burden, and elevated inflammatory markers. With a median follow-up of 7.4 months, patients with low mHLA-DR Dâ7 exhibited a poorer duration of response and survival than the higher mHLA-DR Dâ7 group. For toxicity management, tocilizumab was more frequently used in the lowâmHLA-DR Dâ7 group. These data suggest that monocyte dysregulation before LD, characterized by the downregulation of mHLA-DR, correlates with an inflammatory and immunosuppressive tumor environment and is associated with failure of anti-CD19 CAR T cells in patients with R/R LBCL. Modulation of these myeloid cells represents a promising field for improving CAR therapy