Phase I trial of alpha-particle immunotherapy with 225Ac-lintuzumab and low-dose cytarabine in patients age 60 or older with untreated acute myeloid leukemia.

456Objectives: 225Ac-lintuzumab is a radioimmunoconjugate composed of 225Ac, which emits 4 α-particles, linked to a humanized anti-CD33 monoclonal antibody. An initial phase I trial showed that a single infusion of 225Ac-lintuzumab is safe at doses ≤ 111 kBq/kg and has activity in relapsed/refractory acute myeloid leukemia (AML). We conducted a multicenter, phase I dose-escalation trial to determine the maximum tolerated dose (MTD), toxicity, and biological activity of fractionated-dose 225Ac-lintuzumab in combination with low-dose cytarabine (LDAC).Methods: Patients 蠅 60 years with untreated AML not candidates for intensive chemotherapy were eligible. Patients received LDAC 20 mg twice daily for 10 days every 4-6 weeks for up to 12 cycles. During Cycle 1, 2 fractions of 225Ac-lintuzumab were given 1 week apart, beginning 4-7 days following completion of LDAC. To prevent radiation-induced nephrotoxicity, patients were given furosemide while receiving 225Ac-lintuzumab then spironolactone for 1 year afterward. Four dose levels of 225Ac-lintuzumab were studied using a 3+3 design.Results: Eighteen patients (median age, 77 years; range, 68-87) completed therapy. Twelve (67%) had prior myelodysplastic syndrome (MDS), for which 10 (83%) received therapy with hypomethylating agents (n=9) or allogeneic hematopoietic cell transplantation (n=1). Eleven patients (61%) had intermediate-risk and 7 (39%) had poor-risk AML. Median CD33 expression was 81% (range, 30-100%). 225Ac...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Radiopharmaceutical Therapy- Radioimmunotherapy and Radioembolization Source Type: research

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Objectives: Previous retrospective studies demonstrated that circulating tumor cells (CTCs) subtypes correlate with overall survival in patients with pancreatic ductal adenocarcinoma (PDAC). Herein, we report results of a prospective observational study on CTCs dynamics to assess their clinical significance. Methods: The CLUSTER study is a prospective longitudinal study on PDAC CTCs dynamics (NCT02974764). Multiple peripheral blood samples were collected from 200 consecutively enrolled patients with presumed PDAC diagnosis. CTCs were isolated and characterized by immunofluorescence. Results: Two major CTCs subtypes...
Source: Annals of Surgery - Category: Surgery Tags: Papers of the 138Th ASA Annual Meeting Source Type: research
Conclusion: IdeS may represent a groundbreaking new method of desensitization for patients who otherwise might have no hope for receiving a lifesaving transplant.
Source: Annals of Surgery - Category: Surgery Tags: Papers of the 138Th ASA Annual Meeting Source Type: research
Pneumonia is a common cause of respiratory infection, accounting for more than 800,000 hospitalizations in the United States annually. Presenting symptoms of pneumonia are typically cough, pleuritic chest pain, fever, fatigue, and loss of appetite. Children and the elderly have different presenting features of pneumonia, which include headache, nausea, abdominal pain, and absence of one or more of the prototypical symptoms. Knowledge of local bacterial pathogens and their antibiotic susceptibility and resistance profiles is the key for effective pharmacologic selection and treatment of pneumonia.
Source: Primary Care: Clinics in Office Practice - Category: Primary Care Authors: Source Type: research
Publication date: Available online 13 August 2018Source: The Lancet HaematologyAuthor(s): Tapan M Kadia, Jorge Cortes, Farhad Ravandi, Elias Jabbour, Marina Konopleva, Christopher B Benton, Jan Burger, Koji Sasaki, Gautam Borthakur, Courtney D DiNardo, Naveen Pemmaraju, Naval Daver, Alessandra Ferrajoli, Xuemei Wang, Keyur Patel, Jeffrey L Jorgensen, Sa Wang, Susan O'Brien, Sherry Pierce, Carla TuttleSummaryBackgroundFront-line therapy for elderly or unfit patients with acute myeloid leukaemia (AML) remains unsatisfactory with poor outcomes and excessive toxicity. We studied a new low-intensity regimen of cladribine combin...
Source: The Lancet Haematology - Category: Hematology Source Type: research
Introduction: We hypothesized that aromatic microbial metabolites (AMM), such as phenyllactic (PhLA), p-hydroxyphenylacetic (p-HPhAA), and p-hydroxyphenyllactic (p-HPhLA) acids, contribute to the pathogenesis of septic shock. Methods: Clinical and laboratory data of patients with community-acquired pneumonia were obtained on intensive care unit admission and the next day. Patients were divided into two groups based on septic shock presence or absence. The levels of AMM (PhLA, p-HPhAA, p-HPhLA, and their sum, ∑3AMM), catecholamine metabolites (3,4-dihydroxymandelic [DHMA], 3,4-dihydroxyphenylacetic [DOPAC], and hom...
Source: Shock - Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research
Conclusions: Intraperitoneal LPS injection in ApoE3*Leiden mice triggers a profound systemic inflammatory response, but does not increase atherosclerotic plaque area or inflammatory cell density. This model of LPS-induced inflammation in atherosclerosis-prone mice argues against intraplaque alterations as an explanation for acute inflammation-induced cardiovascular event risk.
Source: Shock - Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research
Kai Niu, Yunming Yao, Ming Xiu, Chunjie Guo, Yuanyuan Ge, Jianmeng Wang
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Publication date: September 2018Source: Archives of Cardiovascular Diseases Supplements, Volume 10, Issues 3–4Author(s): Yasmine Benadjaoud, Fanny Bajolle, Olivier Raisky, Damien BonnetObjectiveSingle-ventricular disease with atrioventricular septal defect (AVSD) includes a variety of complex congenital heart defects such as unbalanced AVSD and univentricular hearts with common atrioventricular valve, commonly associated with heterotaxy. Our objective was to describe hard outcomes (death, transplantation) and their predictors in these defects.MethodsWe conducted a retrospective, monocentric review of children with a ...
Source: Archives of Cardiovascular Diseases Supplements - Category: Cardiology Source Type: research
Publication date: September 2018Source: Archives of Cardiovascular Diseases Supplements, Volume 10, Issues 3–4Author(s): Zahra Belhadjer, Diala Khraich, Damien BonnetIntroductionThe dilated cardiomyopathies (DCM) in pediatric patients is a severe disease and is the leading cause of heart transplantation in children. Predictive factors for mortality and transplantation differs from one study to another with a lack of long-term data. The aim of this study is to determine these factors during the follow-up.MethodsWe performed a retrospective monocentric study of patients followed up for DCM. Patients under the age of 18...
Source: Archives of Cardiovascular Diseases Supplements - Category: Cardiology Source Type: research
ConclusionsWe did not find statistical relationship between HT and the clinical factors of age>50 years and DM. Statistical relationship for the dosimetric factors V10 > 90% and V20 > 80% was not found as well. On the contrary, obesity, epidermoid histology and ≥IIIA CS, showed statistical significance for development of HT ≥grade 2.
Source: Reports of Practical Oncology and Radiotherapy - Category: Cancer & Oncology Source Type: research
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