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Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is common after chimeric antigen receptor T-cell (CAR-T) therapy., Objective: This study aimed to assess the impact of preinfusion electroencephalography (EEG) abnormalities and EEG findings at ICANS onset for predicting ICANS risk and severity in 56 adult patients with refractory lymphoma undergoing CAR-T therapy., Study Design: EEGs were conducted at the time of lymphodepleting chemotherapy and shortly after onset of ICANS., Results: Twenty-eight (50%) patients developed ICANS at a median time of 6 days after CAR-T infusion. Abnormal preinfusion EEG was identified as a risk factor for severe ICANS (50% vs. 17%, P = 0.036). Following ICANS onset, EEG abnormalities were detected in 89% of patients [encephalopathy (n = 19, 70%) and/or interictal epileptiform discharges (IEDs) (n = 14, 52%)]. Importantly, IEDs seemed to be associated with rapid progression to higher grades of ICANS within 24 h., Conclusions: If confirmed in a large cohort of patients, these findings could establish the basis for modifying current management guidelines, enabling the identification of patients at risk of neurotoxicity, and providing support for preemptive corticosteroid use in patients with both initial grade 1 ICANS and IEDs at neurotoxicity onset, who are at risk of neurological impairment., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background Aims: There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA - memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment., Methods: Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 10 6 /kg CD45RA - memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2-specific response within the CD45RA - memory T cells and the most frequent human leukocyte antigen typing in the Spanish population., Results: We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events., Conclusions: Adoptive cell therapy with off-the-shelf CD45RA - memory T cells containing SAR-CoV-2-specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia., Trial Registration: NCT04578210., Competing Interests: Declaration of Competing Interest CF, AP-M and BS filed patent PCT/EP2021/076516 on Memory T cells as adoptive cell therapy for viral diseases. All other authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

An unprecedented global social and economic impact as well as a significant number of fatalities have been brought on by the coronavirus disease 2019 (COVID-19), produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute SARS-CoV-2 infection can, in certain situations, cause immunological abnormalities, leading to an anomalous innate and adaptive immune response. While most patients only experience mild symptoms and recover without the need for mechanical ventilation, a substantial percentage of those who are affected develop severe respiratory illness, which can be fatal. The absence of effective therapies when disease progresses to a very severe condition coupled with the incomplete understanding of COVID-19's pathogenesis triggers the need to develop innovative therapeutic approaches for patients at high risk of mortality. As a result, we investigate the potential contribution of promising combinatorial cell therapy to prevent death in critical patients., Competing Interests: AP-M, CF and BS filed patents on this topic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gonzaga, Andreu, Hernández-Blasco, Meseguer, Al-Akioui-Sanz, Soria-Juan, Sanjuan-Gimenez, Ferreras, Tejedo, Lopez-Lluch, Goterris, Maciá, Sempere-Ortells, Hmadcha, Borobia, Vicario, Bonora, Aguilar-Gallardo, Poveda, Arbona, Alenda, Tarín, Marco, Merino, Jaime, Ferreres, Figueira, Cañada-Illana, Querol, Guerreiro, Eguizabal, Martín-Quirós, Robles-Marhuenda, Pérez-Martínez, Solano and Soria.)

Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P < .05) and less refractoriness (4.5% vs 14.1%; P < .05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P < .05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P < .001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Homozygous familial hypercholesterolaemia (HoFH) is a rare, genetic disorder of abnormally high levels of low-density lipoprotein cholesterol (LDL-C) requiring aggressive interventions to retard the evolution of atherosclerotic cardiovascular disease. We treated two brothers (ages 46 years and 47 years) with HoFH with statins, lipoproteinapheresis (LA) and the microsomal triglyceride transfer protein inhibitor lomitapide. Both brothers carried the p.Thr434Arg homozygous LDLR mutation and had childhood total cholesterol levels >700 mg/dL. Inter-LA LDL-C levels remained high; therefore, they were given escalating doses of oral lomitapide (5-10 mg/day). One brother was able to maintain LDL-C levels <70 mg/dL and stop LA. Lomitapide was well tolerated, with only an episode of headache requiring dose reduction from 40 mg/day to 20 mg/day in one patient. In two HoFH cases, lomitapide was an effective and well-tolerated adjunct therapy. Lomitapide doses required to maintain LDL-C goal levels appear to be lower in clinical practice than in clinical trials., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Objective: The aim of our study is to analyze the effect and security of low-density lipoproteins (LDL) apheresis in familial hypercholesterolemia (FH) subjects who did not response to conventional intensive optimized medical treatment., Patients and Methods: Seven heterozygous FH subjects and one homozygous apoB familial defective were studied. All subjects were on secondary prevention with highest statins doses in association with other hypolipemiant drugs; the mean LDL-C reduction was 20%. All of them were treated with LDL apheresis (immunoabsorption) for a mean of 4.25 years., Results: LDL apheresis resulted in a 68.3% decrease in LDL-C and 58.2% in apoB plasma values (P<.001). After an average of 3 years of follow-up, the cardiovascular events disappeared in 4 out of 5 symptomatic patients while in one patient the events were reduced in 75%. Four moderate side effects were reported in 820 apheresis procedures., Conclusions: LDL apheresis is a well-tolerated and safe treatment in FH patients who do not response to intensive conventional optimized medical treatment. The main limitation is its economical cost and low accessibility., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

High-dose chemotherapy supported by autologous stem cell transplant (ASCT) remains the treatment of choice for patients with lymphoma failing first-line chemotherapy. Recent evidence suggests a relationship between the genetic variations in genes involved in DNA repair and the outcome of patients with a number of malignancies. In this work, we retrospectively evaluated the influence of an XRCC1 polymorphism (rs25487) on the treatment results in a series of 73 patients with lymphoma subjected to ASCT. The factors correlated to overall survival were the disease status at transplant and XRCC1 genotype. Carriers of a mutant A allele had a two-fold higher risk of death than those with the wild-type genotype. In addition, patients harboring one or two copies of the A allele (GA/AA) were 4.5-fold more likely to develop therapy-related acute myeloid (t-AML). Thus, the cumulative probability of t-AML at 10 years was 37 ± 13% in patients with the mutant A allele as compared to 8.5 ± 6% in the remaining cases (p = 0.04). Our findings suggest that genetic variation in the DNA repair gene XRCC1 may play a role in the results of transplant in patients with lymphoma.

Background: Between 30% and 60% of patients with thrombotic thrombocytopenic purpura (TTP) relapse and mortality remains at 15-20%. Limited clinical data suggest that the administration of anti-CD20 antibody (rituximab) may be useful in preventing acute refractory and chronic relapsing TTP., Design and Methods: We studied the clinical response to rituximab in 24 adult patients (median age 42 years, range 24-72 years) from 15 Spanish centers with an acute refractory (14 patients) or acute relapsing (10 patients) episode of idiopathic TTP. On admission, every patient received daily plasma exchange (PE). Rituximab was administered at a dose of 375 mg/m(2) weekly for a median of 13 days (range 0-57 days) after starting PE for a median of 4 doses (range 1-8 doses)., Results: No severe acute or delayed toxicity was observed in the patients treated with rituximab. Three (12.5%) patients died because of TTP-related causes. The remaining 21 (87.5%) patients achieved complete remission in a median of 21 days (range 2-35 days) after initiating rituximab. After a median follow-up of 30 months (range 7.5-74 months), 18 patients are in remission and 3 patients have relapsed at 7, 29, and 29 months., Conclusions: Rituximab appears to be a safe, effective therapy and has a high response rate for the treatment of acute refractory or relapsing idiopathic TTP in adult patients., (Copyright © 2010 Elsevier Ltd. All rights reserved.)