Blood
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Multicenter Study Clinical Trial
Activity of Transgene-Produced B-Domain Deleted Factor VIII in Human Plasma Following AAV5 Gene Therapy.
Adeno-associated virus (AAV)-based gene therapies can restore endogenous factor VIII (FVIII) expression in hemophilia A (HA). AAV vectors typically use a B-domain-deleted FVIII transgene, such as human FVIII-SQ in valoctocogene roxaparvovec (AAV5-FVIII-SQ). Surprisingly, the activity of transgene-produced FVIII-SQ was between 1.3 and 2.0 times higher in one-stage clot (OS) assays than in chromogenic-substrate (CS) assays, whereas recombinant FVIII-SQ products had lower OS than CS activity. ⋯ A correlation with joint bleeds suggested that both OS and CS assay remained clinically meaningful to distinguish hemophilic from nonhemophilic FVIII activity levels. During clinical development, the CS activity was chosen as a surrogate end point to conservatively assess hemostatic efficacy and enable comparison with recombinant FVIII-SQ products. Relevant trials are registered on clinicaltrials.gov as #NCT02576795 and #NCT03370913 and, respectively, on EudraCT (European Union Drug Regulating Authorities Clinical Trials Database; https://eudract.ema.europa.eu) as #2014-003880-38 and #2017-003215-19.
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Multicenter Study Observational Study
Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19.
Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. ⋯ All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.
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One to 2 pregnant women in 1000 will experience venous thromboembolism (VTE) during pregnancy or postpartum. Pulmonary embolism (PE) is a leading cause of maternal mortality, and deep vein thrombosis leads to maternal morbidity, with postthrombotic syndrome potentially diminishing quality of life for a woman's lifetime. However, the evidence base for pregnancy-related VTE management remains weak. ⋯ Management of delivery, including type of analgesia, requires a multidisciplinary approach and depends on local preferences and patient-specific conditions. Several options are possible, including waiting for spontaneous delivery with temporary LMWH interruption. Prophylaxis for recurrent VTE prevention in subsequent pregnancies is indicated in most women with a history of VTE.