Tagraxofusp and anti-CD123 in blastic plasmacytoid dendritic cell neoplasm: a new hope.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy, characterized by poor prognosis if treated with conventional therapy. Allogenic hematologic stem cell transplant can improve survival and can be curative, but it is available in a small percentage of patients given that the median age at diagnosis is 70 years. In this scenario it is assumed that only the development of precision medicine-driven therapy will change BPDCN patient prognosis. CD123 (the α-subunit of interleukin (IL)-3 receptor) is over-expressed on BPDCN cells surface and seems to be the ideal marker to develop antibody-based therapies. Tagraxofusp (Elzonris®), a recombinant immunotoxin consisting of human interleukin-3 fused to a truncated diphtheria toxin, has been approved by FDA in December 2018 for the treatment of BPDCN in adult and pediatric patients. tagraxofusp has shown promising clinical activity, with a high overall response rate and quite manageable safety profile even in elderly patients. It seems to improve overall survival too, but comparative trials are necessary to confirm this. Adverse events are commonly reported and the most important are transaminitis, thrombocytopenia and capillary leak syndrome (CLS). Therefore, to prevent the onset of severe CLS is recommended to reserve tagraxofusp for patients with preserved hepatic and cardiac functions, and to strictly observe serum albumin level. Further studies are required to resolve many several unanswered questions about tagraxofusp. In this review, we will resume and discuss pharmacological characteristic of tagraxofusp, results of clinical trials leading to its approval by FDA in 2018 and future perspectives about its use in BPDCN and other hematological malignancies.

In vivo microvascular actions of Artemisia vulgaris L. in a model of ischemia-reperfusion injury in the rat intestinal mesentery.

Water extract fractions of leaves from Artemisia vulgaris L. (commonly known as mugwort) were tested for their effects on tissue damage brought about by ischemia-reperfusion injury in the rat mesentery. Male Sprague-Dawley rats, 200-300 grams in weight were divided into two groups, control and treatment (AV) group. All rats were anesthetized with ketamine HCl administered intramuscularly, tracheotomized and cannulated in one carotid artery and one jugular vein. After a midline abdominal incision, the mesenteric area was exteriorized and observed using videomicroscopy. After baseline observations of systemic blood pressure, heart rate, venular diameters and leukocyte adhesion along venules, the mesenteric artery and vein were occluded for 10 minutes. Prior to occlusion, A. vulgaris-treated animals were given a bolus injection of a 1% w/v solution of extracts, while the control group received saline. Monastral Blue dye was also administered before the occlusion at a dose of 30 mg/kg via the jugular vein in order to assess transendothelial leakage. Hemodynamic and cellular parameters were measured immediately after the release of occlusion and at 10 minute intervals thereafter. Results show that the extracts had no significant effects on mean blood pressures and heart rates, but appeared to significantly reduce leukocyte adherence and transendothelial leakage while improving flow in the ischemia-reperfused organ. The extract fractions contain yomogin, which has been previously shown to inhibit iNOS activity, and may therefore explain the anti-inflammatory property of the plant.