Clinical Utilization of Chimeric Antigen Receptor T Cells in B Cell Acute Lymphoblastic Leukemia: An Expert Opinion from the European Society for Blood and Marrow Transplantation and the American Society for Blood and Marrow Transplantation.

On August 30, 2017 the US Food and Drug Administration approved tisagenlecleucel (Kymriah; Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present, ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring, and disease assessments. To address these issues experts representing the American Society for Blood and Marrow Transplant, the European Society for Blood and Marrow Transplantation, the International Society of Cell and Gene Therapy, and the Foundation for the Accreditation of Cellular Therapy formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.

Optimal Lymphadenectomy in Small Bowel Neuroendocrine Tumors: Analysis of the NCDB.

BACKGROUND: Current National Comprehensive Cancer Network guidelines for resectable small bowel neuroendocrine tumors (NETs) recommend regional lymphadenectomy. However, no consensus exists on the optimal nodal harvest. METHODS: The National Cancer Database was queried for patients with resectable small bowel NETs (1998-2013). Patients with metastatic disease and missing lymph node harvest data were excluded. We performed logistic regression of factors determining nodal positivity and multivariable survival analyses. RESULTS: Of 11,852 patients, 81.8% underwent lymphadenectomy. 79.3% were node positive (N+) and 46.9% of patients had tumors < 1 cm. Independent predictors of N+ were large tumor size, ileal location, and neuroendocrine carcinoma histology. Logistic regression found no difference between observed and expected proportions of N+ patients with lymphadenectomy greater than or equal to eight nodes. Lower metastatic node ratio predicted improved survival on multivariable analysis and is associated with high-volume institutions. CONCLUSION: Small bowel NETs have high rates of nodal metastasis, even in patients with small tumors, and many patients do not undergo lymphadenectomy despite the clear benefit. Lymphadenectomy of eight nodes is optimal to identify N+ patients. Additionally, minimizing metastatic node ratio with complete regional lymphadenectomy is associated with improved survival in these patients.

Flexibility transition and guest-driven reconstruction in a ferroelastic metal-organic framework†Electronic supplementary information (ESI) available: Atomic coordinates and lattice parameter data. CCDC 1016797. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4ce01572jClick here for additional data file.

The metal-organic framework copper(i) tricyanomethanide, Cu(tcm), undergoes a ferroelastic transition on cooling below Tf = 240 K. Thermal expansion measurements reveal an order-of-magnitude variation in framework flexibility across Tf. The low-temperature phase α-Cu(tcm) exhibits colossal positive and negative thermal expansion that is the strongest ever reported for a framework material. On exposure to acetonitrile, Cu(tcm) undergoes a reconstructive solid-phase transition to acetonitrilocopper(i) tricyanomethanide. This transition can be reversed by heating under vacuum. Infrared spectroscopy measurements are sensitive to the phase change, suggesting that Cu(tcm) may find application in solid-phase acetonitrile sensing.