title: Chimeric Antigen Receptor T Cells in Hematologic Malignancies.
abstract: Patients with B-cell hematologic malignancies who progress through first- or second-line chemotherapy have a poor prognosis. Early clinical trials with autologous anti-CD19 chimeric antigen receptor (CAR) T cells have demonstrated promising results for patients who have relapsed or refractory disease. Lymphodepleting conditioning regimens, including cyclophosphamide, fludarabine, pentostatin, bendamustine, interleukin-2, and total body irradiation, are often administered before the infusion of CAR T cells, allowing for greater T-cell expansion. The major toxicity associated with CAR T-cell infusions is cytokine release syndrome (CRS), a potentially life-threatening systemic inflammatory disorder. The quick onset and progression of CRS require rapid detection and intervention to reduce treatment-related mortality. Management with tocilizumab can help ameliorate the symptoms of severe CRS, allowing steroids, which diminish the expansion and persistence of CAR T cells, to be reserved for tocilizumab-refractory patients. Other toxicities of CAR T-cell therapy include neutropenia and/or febrile neutropenia, infection, tumor lysis syndrome, neurotoxicity and nausea/vomiting. A review of patients' medications is imperative to eliminate medications that may contribute to treatment-related toxicities. Studies are ongoing to help optimize patient selection, preparation, safety, and management of individuals receiving CAR T cells. Long-term follow-up will help establish the place of CAR T cells in therapy.
authors.affiliation: Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Brandon R
authors.initials: BR
authors.lastname: Shank
authors.affiliation: Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Bryan
authors.initials: B
authors.lastname: Do
authors.affiliation: Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Sevin
authors.affiliation: Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sheree E
authors.initials: SE
authors.lastname: Chen
authors.affiliation: Division of Cancer Medicine, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sattva S
authors.initials: SS
authors.lastname: Neelapu
authors.affiliation: Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sandra B
authors.initials: SB
authors.lastname: Horowitz
mesh_terms: D018941:Antigens, CD19 / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000628:therapy*; D006801:Humans; D018579:Patient Selection; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell; D013577:Syndrome; D013601:T-Lymphocytes / Q000637:transplantation*; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome
chemical_list: D018941:Antigens, CD19; D000970:Antineoplastic Agents; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell
keywords: chimeric antigen receptor T cells; hematologic malignancies; immunology