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H3K27M-mutant diffuse midline gliomas (DMGs) express high levels of the disialoganglioside GD2 (ref. 1). Chimeric antigen receptor-modified T cells targeting GD2 (GD2-CART) eradicated DMGs in preclinical models2. Arm A of Phase I trial no. NCT04196413(ref. 3) administered one intravenous (IV) dose of autologous GD2-CART to patients with H3K27M-mutant pontine (DIPG) or spinal DMG (sDMG) at two dose levels (DL1, 1 × 106kg−1; DL2, 3 × 106kg−1) following lymphodepleting chemotherapy. Patients with clinical or imaging benefit were eligible for subsequent intracerebroventricular (ICV) intracranial infusions (10–30 × 106GD2-CART). Primary objectives were manufacturing feasibility, tolerability and the identification of maximally tolerated IV dose. Secondary objectives included preliminary assessments of benefit. Thirteen patients enroled, with 11 receiving IV GD2-CART on study (n= 3 DL1 (3 DIPG); n= 8 DL2 (6 DIPG, 2 sDMG)). GD2-CART manufacture was successful for all patients. No dose-limiting toxicities occurred on DL1, but three patients experienced dose-limiting cytokine release syndrome on DL2, establishing DL1 as the maximally tolerated IV dose. Nine patients received ICV infusions, with no dose-limiting toxicities. All patients exhibited tumour inflammation-associated neurotoxicity, safely managed with intensive monitoring and care. Four patients demonstrated major volumetric tumour reductions (52, 54, 91 and 100%), with a further three patients exhibiting smaller reductions. One patient exhibited a complete response ongoing for over 30 months since enrolment. Nine patients demonstrated neurological benefit, as measured by a protocol-directed clinical improvement score. Sequential IV, followed by ICV GD2-CART, induced tumour regressions and neurological improvements in patients with DIPG and those with sDMG.

A case series is presented of five overweight or obese patients with confirmed coronavirus disease 2019 (COVID-19) in South Miami, Florida, United States. A multitude of coagulation parameters was suggestive of a hypercoagulable state among the hospitalized COVID-19 patients. This article reports various manifestations of hypercoagulable states in overweight and obese patients, such as overt bleeding consistent with disseminated intravascular coagulation, venous thromboembolism, gastrointestinal bleeding as well as retroperitoneal hematoma. All of the required admission to the intensive care unit and subsequently patients died. The characteristics of COVID-19-associated coagulopathy are atypical and warrant a further understanding of the pathophysiology to improve clinical outcomes, specifically in overweight or obese patients.