Mayo Clinic

About: Mayo Clinic is a healthcare organization based out in Rochester, Minnesota, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 63387 authors who have published 169578 publications receiving 8114006 citations.

Chimeric antigen receptor T-cell therapy — assessment and management of toxicities

Abstract: Immunotherapy using T cells genetically engineered to express a chimeric antigen receptor (CAR) is rapidly emerging as a promising new treatment for haematological and non-haematological malignancies. CAR-T-cell therapy can induce rapid and durable clinical responses, but is associated with unique acute toxicities, which can be severe or even fatal. Cytokine-release syndrome (CRS), the most commonly observed toxicity, can range in severity from low-grade constitutional symptoms to a high-grade syndrome associated with life-threatening multiorgan dysfunction; rarely, severe CRS can evolve into fulminant haemophagocytic lymphohistiocytosis (HLH). Neurotoxicity, termed CAR-T-cell-related encephalopathy syndrome (CRES), is the second most-common adverse event, and can occur concurrently with or after CRS. Intensive monitoring and prompt management of toxicities is essential to minimize the morbidity and mortality associated with this potentially curative therapeutic approach; however, algorithms for accurate and consistent grading and management of the toxicities are lacking. To address this unmet need, we formed a CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group, comprising investigators from multiple institutions and medical disciplines who have experience in treating patients with various CAR-T-cell therapy products. Herein, we describe the multidisciplinary approach adopted at our institutions, and provide recommendations for monitoring, grading, and managing the acute toxicities that can occur in patients treated with CAR-T-cell therapy.

History of the Rochester Epidemiology Project

Abstract: The Rochester Epidemiology Project is a unique medical records-linkage system that encompasses the care delivered to residents of Rochester and Olmsted County, Minnesota. It is the creation of Dr. Leonard T. Kurland, who envisioned the population-based data resource that would result from combining the clinical documentation developed by the Mayo Clinic with that obtained by other community providers, most notably the Olmsted Medical Group and its affiliated Olmsted Community Hospital. Kurland built on the Mayo unit medical record system that was designed by Dr. Henry S. Plummer in 1907 and on the medical and surgical indexing systems introduced by Dr. Joseph Berkson in 1935. By affording access to details of the medical care given to local residents, the Rochester Epidemiology Project is able to provide accurate incidence data for almost any serious condition and to support population-based analytic studies of disease causes and outcomes. Thus, epidemiologic studies of a wide array of disorders have been possible and have culminated in almost 900 publications since the system was organized in 1966. Olmsted County is one of the few places in the world where the occurrence and natural history of diseases can be accurately described and analyzed in a defined population for a half century or more.

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

Abstract: BackgroundPatients with acute myeloid leukemia (AML) and a FLT3 mutation have poor outcomes. We conducted a phase 3 trial to determine whether the addition of midostaurin — an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation — to standard chemotherapy would prolong overall survival in this population. MethodsWe screened 3277 patients, 18 to 59 years of age, who had newly diagnosed AML for FLT3 mutations. Patients were randomly assigned to receive standard chemotherapy (induction therapy with daunorubicin and cytarabine and consolidation therapy with high-dose cytarabine) plus either midostaurin or placebo; those who were in remission after consolidation therapy entered a maintenance phase in which they received either midostaurin or placebo. Randomization was stratified according to subtype of FLT3 mutation: point mutation in the tyrosine kinase domain (TKD) or internal tandem duplication (ITD) mutation with either a high ratio (>0.7) or a low ratio (0.05 to 0.7) of muta...