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Tracking Inflammation in CAR-T Therapy: The Emerging Role of Serum Amyloid A (SAA)
by
Pansini, Ilaria
, Sica, Simona
, Baroni, Silvia
, Chiusolo, Patrizia
, Piccirillo, Nicola
, Viscovo, Marcello
, Sorà, Federica
, Galli, Eugenio
, Corrente, Alessandro
in
Amyloid
/ B-cell lymphoma
/ Biomarkers
/ Care and treatment
/ Cell therapy
/ Chimeric antigen receptors
/ Cytokine storm
/ Development and progression
/ Disease
/ Ferritin
/ Fibrinogen
/ Inflammation
/ Interleukin 6
/ Interleukins
/ Lymphocytes
/ Lymphocytes B
/ Lymphocytes T
/ Lymphoma
/ Malignancy
/ Patients
/ Procalcitonin
/ Statistical analysis
/ T cells
/ Toxicity
2025
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Tracking Inflammation in CAR-T Therapy: The Emerging Role of Serum Amyloid A (SAA)
by
Pansini, Ilaria
, Sica, Simona
, Baroni, Silvia
, Chiusolo, Patrizia
, Piccirillo, Nicola
, Viscovo, Marcello
, Sorà, Federica
, Galli, Eugenio
, Corrente, Alessandro
in
Amyloid
/ B-cell lymphoma
/ Biomarkers
/ Care and treatment
/ Cell therapy
/ Chimeric antigen receptors
/ Cytokine storm
/ Development and progression
/ Disease
/ Ferritin
/ Fibrinogen
/ Inflammation
/ Interleukin 6
/ Interleukins
/ Lymphocytes
/ Lymphocytes B
/ Lymphocytes T
/ Lymphoma
/ Malignancy
/ Patients
/ Procalcitonin
/ Statistical analysis
/ T cells
/ Toxicity
2025
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Tracking Inflammation in CAR-T Therapy: The Emerging Role of Serum Amyloid A (SAA)
by
Pansini, Ilaria
, Sica, Simona
, Baroni, Silvia
, Chiusolo, Patrizia
, Piccirillo, Nicola
, Viscovo, Marcello
, Sorà, Federica
, Galli, Eugenio
, Corrente, Alessandro
in
Amyloid
/ B-cell lymphoma
/ Biomarkers
/ Care and treatment
/ Cell therapy
/ Chimeric antigen receptors
/ Cytokine storm
/ Development and progression
/ Disease
/ Ferritin
/ Fibrinogen
/ Inflammation
/ Interleukin 6
/ Interleukins
/ Lymphocytes
/ Lymphocytes B
/ Lymphocytes T
/ Lymphoma
/ Malignancy
/ Patients
/ Procalcitonin
/ Statistical analysis
/ T cells
/ Toxicity
2025
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Tracking Inflammation in CAR-T Therapy: The Emerging Role of Serum Amyloid A (SAA)
Journal Article
Tracking Inflammation in CAR-T Therapy: The Emerging Role of Serum Amyloid A (SAA)
2025
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Overview
Background: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of relapsed/refractory large B-cell lymphoma (LBCL), but its administration is often complicated by cytokine release syndrome (CRS). Interleukin-6 (IL-6) is widely used to monitor CRS, though its clinical value diminishes after tocilizumab administration. We aimed to evaluate serum amyloid A (SAA), a dynamic acute-phase reactant, as a treatment-independent biomarker of inflammation and toxicity in CAR-T recipients. Methods: This retrospective study included 43 adults with LBCL treated with axicabtagene ciloleucel. SAA and other inflammatory markers were assessed from lymphodepletion through day +11 post-infusion. CRS and ICANS were graded per ASTCT criteria. Statistical analyses included Mann–Whitney U tests, Spearman’s correlation, and ROC curve analysis to evaluate predictive performance. Results: SAA levels peaked at day +4 and normalized by day +11, displaying wave-like kinetics. Levels were significantly higher in patients with any-grade CRS at early timepoints but showed no association with ICANS. SAA correlated strongly with CRP, suPAR, sST2, fibrinogen, ferritin, procalcitonin, and IL-6. Compared to IL-6, SAA was more predictive of CRS at day +2 and +4, and unaffected by tocilizumab. Baseline SAA also correlated with the mEASIX score, suggesting linkage to endothelial stress. Non-responders at 3-month PET had higher baseline SAA than responders (196.0 vs. 17.7 mg/L, p = 0.036), with ROC analysis yielding an AUC of 0.74 and an optimal threshold of 79.8 mg/L. Conclusions: SAA is a robust and dynamic marker of systemic inflammation, with potential utility in both toxicity monitoring and response prediction in the CAR-T setting. Its independence from IL-6 modulation positions it as a promising biomarker for future integration into clinical algorithms.
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