RESUMO
Persistent COVID-19 is a well recognized issue of concern in patients with hematological malignancies. Such patients are not only at risk of mortality due to the infection itself, but are also at risk of suboptimal malignancy-related outcomes because of delays and terminations of chemotherapy. We report two lymphoma patients with heavily pretreated persistent COVID-19 in which ensitrelvir brought about radical changes in the clinical course leading to rapid remissions. Patient 1 was on ibrutinib treatment for mantle cell lymphoma when he developed COVID-19 pneumonia which was severe and ongoing for 2 months despite therapy with molnupiravir, multiple courses of remdesivir, one course of sotrovimab, tocilizumab, and steroids. Patient 2 was administered R-CHOP therapy for diffuse large B-cell lymphoma when he developed COVID-19 which was ongoing for a month despite treatment with multiple courses of remdesivir and one course of sotrovimab. A 5-day administration of ensitrelvir promptly resolved the persistent COVID-19 accommodated by negative conversions of RT-qPCR tests in both patients within days. Ensitrelvir is a novel COVID-19 therapeutic that accelerates viral clearance through inhibition of the main protease of SARS-CoV-2, 3-chymotrypsin-like protease, which is vital for viral replication. Ensitrelvir is a promising treatment approach for immunocompromised lymphoma patients suffering from persisting and severe COVID-19.
Assuntos
COVID-19 , Neoplasias Hematológicas , Indazóis , Linfoma Difuso de Grandes Células B , Triazinas , Triazóis , Masculino , Humanos , Adulto , COVID-19/complicações , SARS-CoV-2RESUMO
PURPOSE: Chemotherapy for the hemodialysis (HD) patient is a challenging situation because it requires special considerations including dose modifications and timing of drug administration in relation with HD sessions. Polaltuzumab vedotin (PV), an antibody-drug conjugate in which monomethyl auristatin E (MMAE) is linked to an anti-CD79b monoclonal antibody, is an extremely promising therapeutic for treating diffuse large B cell lymphoma (DLBCL), but the pharmacokinetics are unknown in HD patients. METHODS: We carried out pharmacokinetic studies of PV when administered at 1.2 mg/kg to a DLBCL patient on HD, and compared the results with that of non-HD patients. PV was administered in conjunction with bendamustine and rituximab. RESULTS: Serum concentration-time curves of both antibodyconjugated and unconjugated MMAE in the presented HD patient were similar compared to that of non-HD patients. We also demonstrate that elimination of both antibody-conjugated and unconjugated MMAE through HD is limited. PV administration at 1.2 mg/kg to an HD patient was also clinically feasible, and no signs of peripheral neuropathy were observed. CONCLUSIONS: PV therapy may be a relatively safe treatment method for DLBCL patients on HD.
Assuntos
Imunoconjugados , Linfoma Difuso de Grandes Células B , Humanos , Anticorpos Monoclonais , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Imunoconjugados/efeitos adversos , Rituximab , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Silica nanoparticles (SiNPs) are produced on an industrial scale and used in various fields including health care, because silica is stable, inexpensive, and easy to handle. Despite these benefits, there is concern that exposure to SiNPs may lead to adverse effects in certain types of cells or tissues, such as hemolysis, immune responses, and developmental abnormalities in the brain and developing embryos. Although investigations on the toxicity of SiNPs against neurons are essential for medicinal use, only a few studies have assessed the direct effects of SiNPs on cells derived from the central nervous system. In this study, we investigated the toxic effects of SiNPs on primary cultures of hippocampal cells, using SiNPs with diameters of 10-1500 nm. We showed that treatment with SiNPs caused oxidative stress and cell death. Furthermore, we found that these cytotoxicities were dependent on the particle size, concentration, and surface charge of SiNPs, as well as the treatment temperature. The toxicity was reduced by SiNP surface functionalization or protein coating and by pretreating cells with an antioxidant, suggesting that contact-induced oxidative stress may be partially responsible for SiNP-induced cell death. These data will be valuable for utilizing SiNPs in biomedical applications.