Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study

In older patients with acute myeloid leukemia (AML), the prevention of relapse has remained one of the major therapeutic challenges, with more than 75% relapses after complete remission. The anti-CD33 immunotoxin conjugate gemtuzumab ozogamicin (GO) has shown antileukemic remission induction activity in patients with relapsed AML. Patients with AML or refractory anemia with excess blasts in first complete remission attained after intensive induction chemotherapy were randomized between 3 cycles of GO (6 mg/m(2) every 4 weeks) or no postremission therapy (control) to assess whether GO would improve outcome. The 2 treatment groups (113 patients receiving GO vs 119 control patients) were comparable with regard to age (60-78 years, median 67 years), performance status, and cytogenetics. A total of 110 of 113 received at least 1 cycle of GO, and 65 of 113 patients completed the 3 cycles. Premature discontinuation was mainly attributable to incomplete hematologic recovery or intercurrent relapse. Median time to recovery of platelets 50 x 10(9)/L and neutrophils 0.5 x 10(9)/L after GO was 14 days and 20 days. Nonhematologic toxicities were mild overall, but there was 1 toxic death caused by liver failure. There were no significant differences between both treatment groups with regard to relapse probabilities, nonrelapse mortality, overall survival, or disease-free survival (17% vs 16% at 5 years). Postremission treatment with GO in older AML patients does not provide benefits regarding any clinical end points. The HOVON-43 study is registered at The Netherlands Trial Registry (number NTR212) and at http://www.controlled-trials.com as ISRCTN77039377.

Relationship between the logistic EuroSCORE and the Society of Thoracic Surgeons Predicted Risk of Mortality score in patients implanted with the CoreValve ReValving system--a Bern-Rotterdam Study

Background Surgical risk scores, such as the logistic EuroSCORE (LES) and Society of Thoracic Surgeons Predicted Risk of Mortality (STS) score, are commonly used to identify high-risk or “inoperable” patients for transcatheter aortic valve implantation (TAVI). In Europe, the LES plays an important role in selecting patients for implantation with the Medtronic CoreValve System. What is less clear, however, is the role of the STS score of these patients and the relationship between the LES and STS. Objective The purpose of this study is to examine the correlation between LES and STS scores and their performance characteristics in high-risk surgical patients implanted with the Medtronic CoreValve System. Methods All consecutive patients (n = 168) in whom a CoreValve bioprosthesis was implanted between November 2005 and June 2009 at 2 centers (Bern University Hospital, Bern, Switzerland, and Erasmus Medical Center, Rotterdam, The Netherlands) were included for analysis. Patient demographics were recorded in a prospective database. Logistic EuroSCORE and STS scores were calculated on a prospective and retrospective basis, respectively. Results Observed mortality was 11.1%. The mean LES was 3 times higher than the mean STS score (LES 20.2% ± 13.9% vs STS 6.7% ± 5.8%). Based on the various LES and STS cutoff values used in previous and ongoing TAVI trials, 53% of patients had an LES ≥15%, 16% had an STS ≥10%, and 40% had an LES ≥20% or STS ≥10%. Pearson correlation coefficient revealed a reasonable (moderate) linear relationship between the LES and STS scores, r = 0.58, P < .001. Although the STS score outperformed the LES, both models had suboptimal discriminatory power (c-statistic, 0.49 for LES and 0.69 for STS) and calibration. Conclusions Clinical judgment and the Heart Team concept should play a key role in selecting patients for TAVI, whereas currently available surgical risk score algorithms should be used to guide clinical decision making.

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10 ? ? ). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

Evaluation of the second generation of a bioresorbable everolimus drug-eluting vascular scaffold for treatment of de novo coronary artery stenosis: six-month clinical and imaging outcomes

The first generation of the bioresorbable everolimus drug-eluting vascular scaffold showed signs of shrinkage at 6 months, which largely contributed to late luminal loss. Nevertheless, late luminal loss was less than that observed with bare metal stents. To maintain the mechanical integrity of the device up to 6 months, the scaffold design and manufacturing process of its polymer were modified.

A comparison of the conformability of everolimus-eluting bioresorbable vascular scaffolds to metal platform coronary stents

The aim of this study was to assess the differences in terms of curvature and angulation of the treated vessel after the deployment of either a metallic stent or a polymeric scaffold device.

Cytarabine dose for acute myeloid leukemia

Cytarabine (ara-C) is an important drug in the treatment of acute myeloid leukemia (AML). High-dose cytarabine (2000 to 3000 mg per square meter of body-surface area) is toxic but results in higher rates of relapse-free survival than does the conventional dose of 100 to 400 mg per square meter. Intermediate dose levels have not been thoroughly evaluated.

Serial in vivo intravascular ultrasound-based echogenicity changes of everolimus-eluting bioresorbable vascular scaffold during the first 12 months after implantation insights from the ABSORB B trial

This study sought to investigate quantitative and homogeneity differential echogenicity changes of the ABSORB scaffold (1.1) during the first year after implantation.

Head-to-head comparison of the neointimal response between metallic and bioresorbable everolimus-eluting scaffolds using optical coherence tomography

This study sought to compare the neointimal response of metallic everolimus drug-eluting stents (DES) and polymeric everolimus bioresorbable vascular scaffolds (BVS) by optical coherence tomography at 1 year.

Evaluation of the second generation of a bioresorbable everolimus-eluting vascular scaffold for the treatment of de novo coronary artery stenosis: 12-month clinical and imaging outcomes

The aim of this study was to demonstrate that the prevention of early scaffold area shrinkage of the ABSORB BVS (Rev.1.1, Abbott Vascular, Santa Clara, California) was sustained and not simply delayed by a few months.

Serial analysis of the malapposed and uncovered struts of the new generation of everolimus-eluting bioresorbable scaffold with optical coherence tomography

The aim of this study is to assess the serial changes in strut apposition and coverage of the bioresorbable vascular scaffolds (BVS) and to relate this with the presence of intraluminal masses at 6 months with optical coherence tomography (OCT).

Angiographic geometric changes of the lumen arterial wall after bioresorbable vascular scaffolds and metallic platform stents at 1-year follow-up

The aim of this study was to compare the angiographic changes in coronary geometry of the bioresorbable vascular scaffolds (BVS) and metallic platform stent (MPS) between baseline and follow-up.