Citations

Abstract Chemotherapy-related myeloid neoplasia (t-MN) is a significant late toxicity concern after cancer therapy. In the randomized intergroup phase 3 E2997 trial, initial therapy of chronic lymphocytic leukemia with fludarabine plus cyclophosphamide (FC) compared with fludarabine alone yielded higher complete and overall response rates and longer progression-free, but not overall, survival. Here, we report t-MN incidence in 278 patients enrolled in E2997 with a median 6.4-year follow-up. Thirteen cases (4.7%) of t-MN occurred at a median of 5 years from initial therapy for chronic lymphocytic leukemia, 9 after FC and 4 after fludarabine alone. By cumulative incidence methodology, rates of t-MN at 7 years were 8.2% after FC and 4.6% after fludarabine alone (P = .09). Seven of the 9 cases of t-MN after FC occurred without additional therapy. Abnormalities involving chromosomes 5 or 7 were found in 10 cases, which suggests alkylator involvement. These data suggest that FC may induce more t-MN than fludarabine alone.

BackgroundThe cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)‐42, total‐tau (T‐tau), and phosphorylated‐tau (P‐tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch‐to‐batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.MethodsThe program is open for laboratories using commercially available kits for Aβ, T‐tau, or P‐tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Mölndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples.ResultsForty laboratories participated. Twenty‐six used INNOTEST enzyme‐linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO‐BIA AlzBio3 kit (both measure Aβ‐(1‐42), P‐tau(181P), and T‐tau), and 5 used Meso Scale Discovery with the Aβ triplex (AβN‐42, AβN‐40, and AβN‐38) or T‐tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within‐laboratory precisions differed considerably between biomarkers within individual laboratories.ConclusionsMeasurements of CSF AD biomarkers show large between‐laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.

Background— Effects were compared in patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial of 2 mechanistically different strategies for treatment of hyperglycemia, insulin-sensitizing and insulin-providing strategies, on biomarker profiles reflecting the balance between fibrinolysis and thrombosis and the intensity of inflammation implicated in diabetic vasculopathy. Methods and Results— A total of 2368 patients with type 2 diabetes mellitus and clinically stable, angiographically documented coronary artery disease were randomized to treatment with 1 of the 2 strategies and followed for an average of 5 years. Plasminogen activator inhibitor type 1 antigen and activity, tissue plasminogen activator antigen, fibrinogen, D-dimer, C-reactive protein, insulin, and hemoglobin A 1c were assayed in blood samples acquired at baseline and at 12 regular intervals throughout the follow-up interval. Higher baseline D-dimer, fibrinogen, and C-reactive protein portended a poor prognosis in patients in both groups. In contrast to the insulin-providing strategy, the insulin-sensitizing strategy led to (1) lower plasma insulin; (2) lower plasminogen activator inhibitor type 1 antigen and activity and lower tissue plasminogen activator antigen (known to track with plasminogen activator inhibitor type 1); and (3) lower C-reactive protein and fibrinogen at all intervals after baseline ( P <0.001 for each). Conclusions— The insulin-sensitizing treatment strategy led to changes in biomarker profiles indicative of decreased insulin resistance, an altered balance between thrombosis and fibrinolysis favoring fibrinolysis, and diminished intensity of the systemic inflammatory state, factors that have been associated with cardiovascular risk. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00006305.