Efficacy and safety of bendamustine-containing bridging therapy in R/R LBCL patients receiving CD19 CAR T-cells.

Bridging therapy (BT) after leukapheresis is required in most relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients receiving chimeric antigen receptor (CAR) T cells. Bendamustine-containing regimens are a potential BT option. We aimed to assess if this agent had a negative impact on CAR-T outcomes when it was administered as BT. We included R/R LBCL patients from six centers who received systemic BT after leukapheresis from February 2019 to September 2022; patients who only received steroids or had pre-apheresis bendamustine exposure were excluded. Patients were divided into two BT groups, with and without bendamustine. Separate safety and efficacy analyses were carried out for axi-cel and tisa-cel. Of 243 patients who received BT, bendamustine (benda) was included in 62 (26%). There was a higher rate of BT progressors in the non-benda group (62% vs. 45%, p = 0.02). Concerning CAR-T efficacy, complete responses were comparable for benda versus non-benda BT cohorts with axi-cel (70% vs. 53%, p = 0.12) and tisa-cel (44% vs. 36%, p = 0.70). Also, 12-month progression-free and overall survival were not significantly different between BT groups with axi-cel (56% vs. 43% and 71% vs. 63%) and tisa-cel (25% vs. 26% and 52% vs. 48%); there were no differences when BT response was considered. CAR T-cell expansion for each construct was similar between BT groups. Regarding safety, CRS G ≥3 (6% vs. 6%, p = 0.79), ICANS G ≥3 (15% vs. 17%, p = 0.68), severe infections, and neutropenia post-infusion were comparable among BT regimens. BT with bendamustine-containing regimens is safe for patients requiring disease control during CAR T-cell manufacturing.

Transient acute kidney injury after chimeric antigen receptor T-cell therapy in patients with hematological malignancies.

Background: Acute kidney injury (AKI) occurs in 30% of patients infused with chimeric antigen receptor (CAR) T-cells. The purpose of this study was to identify risk factors and long-term outcomes after AKI in patients who received CAR T-cell therapy. Methods: Medical records of 115 adult patients with R/R hematological malignancies treated with CD19-targeted CAR T-cells at Vall d'Hebron University Hospital between July 2018 and May 2021. Baseline demographic data including age, gender, ethnicity, body mass index (BMI), and co-morbidities, as well as the type of hematological neoplasia and prior lines of therapy were collected. Laboratory parameters including serum creatinine and whole blood hemoglobin were retrospectively reviewed and values were gathered for days +1, +7, +14, +21, and +28 post-infusion. Results: A total of 24/115 (21%) patients developed AKI related to CAR T-cell therapy; 6/24 with AKI over chronic kidney disease (CKD). Two patients had AKI in the context of lymphodepleting (LD) chemotherapy and the other 22 after CAR T-cell infusion, starting at day+1 in 3 patients, day+7 in 13 patients, day +14 in 1 patient, day+21 in 2 patients, and day+28 in 3 patients. Renal function was recovered in 19/24 (79%) patients within the first month after infusion. Male gender, CKD, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with AKI. Male gender, CKD, ICANS grade ≥3 and CRS grade ≥2 were identified as independent risk factors for AKI on multivariable analysis. In terms of the most frequent CAR T-cell related complications, CRS was observed in 95 (82%) patients and ICANS in 33 (29%) patients. Steroids were required in 34 (30%) patients and tocilizumab in 37 (32%) patients. Six (5%) patients were admitted to the intensive care unit (1 for septic shock, 4 for CRS grade ≥2 associated to ICANS grade ≥2, and 1 for CRS grade ≥3). A total of 5 (4.4%) patients died in the first 30 days after CAR T-cell infusion for reasons other than disease progression, including 4 cases of infectious complications and 1 of heart failure. Conclusion: Our results suggest that AKI is a frequent but mild adverse event, with fast recovery in most patients.

18F-FDG-PET/CT response after first-line treatment as a prognostic factor for survival in peripheral T-cell lymphoma: a Spanish retrospective study.

BACKGROUND: An accurate assessment of tumor viability after first-line treatment is critical for predicting treatment failure in peripheral T-cell lymphomas (PTCLs). 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been adopted as the preferred assessment method in clinical trials, but its impact in clinical practice should be examined. This study aims to determine the prognostic significance of18F-FDG-PET/CT for survival following first-line treatment in PTCL patients. RESEARCH DESIGN AND METHODS: Retrospective observational study including 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. RESULTS: Fifty patients were evaluated with18F-FDG-PET/CT following first-line therapy: 58% were18F-FDG-PET/CT-negative and 42% were18F-FDG-PET/CT-positive. Disease progression occurred in 37.9% of18F-FDG-PET/CT-negative patients and in 80.9% of18F-FDG-PET/CT-positive patients (p = 0.0037). Median progression-free survival and overall survival were 67 and 74 months for18F-FDG-PET/CT-negative patients, and 5 (p < 0.0001) and 10 months (p < 0.0001), respectively, in18F-FDG-PET/CT-positive patients. After multivariate analysis, only B symptoms emerged as a negative predictive factor of complete response (RR 7.08; 95% CI 1.60-31.31; p = 0.001). CONCLUSIONS: 18F-FDG-PET/CT identifies high-risk PTCL patients who will have poor prognosis and survival following first-line treatment. However, more research is needed to confirm the best treatment options for PTCL patients.

Compuestos bioactivos derivados de amaranto y quinua / Bioactive components derived from amaranth and quinoa

El amaranto y la quinua son pseudocereales reconocidos por la FAO como cultivos importantes en la soberanía alimentaria para la humanidad por sus propiedades nutricionales. Poseen una alta concentración de proteínas las cuales son consideradas de alto valor nutritivo por contener aminoácidos esenciales como la lisina, el triptófano y la metionina. Se han descrito diferentes actividades biológicas de componentes aislados de amaranto y quinua como actividad antibacteriana, antitumoral, antioxidante, antiin amatoria y antihipertensiva, demostrando que tanto el amaranto como la quinua pueden ser una buena fuente de compuestos bioactivos.

Amaranth and quinoa are pseudo cereals recognized by the FAO as important crops in food sovereignty for humanity due to their nutritional properties. They have a high concentration of proteins, which are considered highly nutritious as containing essential amino acids such as lysine, tryptophan and methionine. Different biological activities isolated from amaranth and quinoa have been described as antibacterial, antitumor, antioxidant, anti-in ammatory and antihypertensive activity components, demonstrating that both amaranth and quinoa can be a good source of bioactive components.

Mantenedor de espacio intra-alveolar: tipo zapata distal: reporte de casos / Maintainer of intra-alveolar space, distal shoe type: case report

El mantenedor de espacio intra – alveolar, tipo zapatilla distal, es una alternativa para prevenir la p‚rdida de espacio cuando se pierde prematuramente la segunda molar decidua y a£n no ha erupcionado el primer molar permanente. Este es un mantenedor fijo con m s ventajas que cualquier aparato removible, porque su permanencia en el lugar indicado es completa, cumpliendo su funci¢n cabalmente. La adaptaci¢n de los ni¤os, a£n los no receptivos, al uso de esta aparatolog¡a, es buena y no ocasiona molestias, ni rechazo. Presentamos dos casos cl¡nicos con resultados favorables.

The “Distal Shoe”, an intra-alveolar space mantainer, is an alternative choice to prevent the loss of space when the primary second molar is lost prematurely and the permanent first molar has still not appeared in mouth. Since this appliance is cemented to the tooth, it does not need the patient’s collaboration, like in removable orthodontic appliances. It has been proved that the use of this appliance does not cause trauma in patients and this has been demonstrated in two non – receptive childs in the following case report.