RESUMEN
Background: Anthracycline cardiotoxicity is a significant clinical challenge. Biomarkers to improve risk stratification and identify early cardiac injury are required. Objectives: The purpose of this pilot study was to prospectively characterize anthracycline cardiotoxicity using cardiovascular magnetic resonance (CMR), echocardiography and MicroRNAs (MiRNAs), and identify baseline predictors of LVEF recovery. Methods: Twenty-four patients (age 56 range 18-75 years; 42 % female) with haematological malignancy scheduled to receive anthracycline chemotherapy (median dose 272 mg/m2 doxorubicin equivalent) were recruited and evaluated at three timepoints (baseline, completion of chemotherapy, and 6 months after completion of chemotherapy) with multiparametric 1.5 T CMR, echocardiography and circulating miRNAs sequencing. Results: Seventeen complete datasets were obtained. CMR left ventricular ejection fraction (LVEF) fell significantly between baseline and completion of chemotherapy (61 ± 3 vs 53 ± 3 %, p < 0.001), before recovering significantly at 6-month follow-up (55 ± 3 %, p = 0.018). Similar results were observed for 3D echocardiography-derived LVEF and CMR-derived longitudinal, circumferential and radial feature-tracking strain. Patients were divided into tertiles according to LVEF recovery (poor recovery, partial recovery, good recovery). CMR-derived mitral annular plane systolic excursion (MAPSE) was significantly different at baseline in patients exhibiting poor LVEF recovery (11.7 ± 1.5 mm) in comparison to partial recovery (13.7 ± 2.7 mm), and good recovery (15.7 ± 3.1 mm; p = 0.028). Furthermore, baseline miRNA-181-5p and miRNA-221-3p expression were significantly higher in this group. T2 mapping increased significantly on completion of chemotherapy compared to baseline (54.0 ± 4.6 to 57.8 ± 4.9 ms, p = 0.001), but was not predictive of LVEF recovery. No changes to LV mass, extracellular volume fraction, T1 mapping or late gadolinium enhancement were observed. Conclusions: Baseline CMR-derived MAPSE, circulating miRNA-181-5p, and miRNA-221-3p were associated with poor recovery of LVEF 6 months after completion of anthracycline chemotherapy, suggesting their potential predictive role in this context. T2 mapping increased significantly on completion of chemotherapy but was not predictive of LVEF recovery.
RESUMEN
Adult-onset Still's disease (AOSD) is an inflammatory disease of unknown aetiology, with no specific diagnostic tests. A 17-year-old female presented with fevers, night sweats and weight loss. Markedly FDG avid lymphadenopathy, and diffuse marrow and splenic uptake were demonstrated on [18F]FDG-PET/CT, most suggestive of lymphoma. After extensive investigations, the working diagnosis of AOSD was made. Other conditions, such AOSD, in addition to lymphoproliferative disorders, should be considered in the differential diagnosis of widespread avid lymphadenopathy in a teenager/young adult.
RESUMEN
BACKGROUND: Chimeric antigen receptor-modified T-cells targeting CD19 (CAR-T19) are licensed for treating relapsed/refractory diffuse large B-cell lymphoma and B-acute lymphoblastic leukemia. Predicting treatment responses and toxicity (e.g., cytokine release syndrome and neurotoxicity) remains a big challenge. CAR-T19 monitoring could increase our understanding of treatment responses and be of relevance to patient management. A robust method for accurate CAR-T19 detection is therefore extremely desirable. METHODS: An assay that uses fluorochrome-conjugated human recombinant soluble CD19 was tested against two commercially available CAR-T19 therapies and a CAR-T19 cell line developed in-house. Precision, concordance, and analyte stability were tested using peripheral blood obtained from CAR-T19-treated patients and controls. RESULTS: The assay showed good accuracy, and had a limit of blank for whole blood samples of 0.13%. Reproducibility and inter-operator concordance were satisfactory (CVs <15%). The assay distinguished CAR-T19 from reactive T-cells in cerebrospinal fluid (CSF) from patients with suspected immune effector cell-associated neurotoxicity syndrome (ICANS), and was adapted to study memory T-cell compartments in treated patients. CONCLUSION: The assay enabled routine monitoring of CAR-T19 in blood and CSF samples. Despite profound cytopenia in many lymphoma patients, results were obtained regularly from only 4 ml of blood. The assay can be adapted easily to characterize the memory and exhaustion status of CAR-T19 and native T-cells. Importantly, it does not rely on CAR construct specificity; thus, it can be used to detect any CD19-targeted CAR cell. Finally, our validation process can serve as a blueprint for other fluorochrome proteins used to detect CAR cells.
