Citations

BackgroundCerebral vasogenic edema (VE) has been reported to occur during antiamyloid immunotherapy. VE may be associated with central nervous system pathology with blood–brain barrier disruptions; however, less is known about the prevalence of naturally occurring VE in patients with Alzheimer's disease (AD).MethodsFluid‐attenuated inversion recovery imaging sequences were obtained from four ongoing multicenter, randomized, double‐blind, placebo‐controlled, phase 3 trials in patients with mild‐to‐moderate AD. The first set of baseline scans was from patients in volumetric magnetic resonance imaging addenda in the Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of Amyloid PaThologY (IDENTITY) studies examining semagacestat, a γ‐secretase inhibitor (cohort 1, n = 621). The second set of baseline scans was from the EXPanding Alzheimer's Disease InvestigaTIONs (EXPEDITION) studies examining solanezumab, an anti‐Aβ monoclonal antibody (cohort 2, n = 2141). Readers were blinded to patient‐identifying information and future treatment. A third set of baseline scans was from the first 700 patients who underwent protocol‐specified magnetic resonance imaging before randomization in the EXPEDITION studies (cohort 3). The analysis used three neuroradiologists: two performed independent primary interpretations and the third was the adjudicator. Readers were blinded to patient information, treatment, protocol, and time point.ResultsFour cases of asymptomatic VE were detected at baseline/screening. Two VE cases were due to underlying extra‐axial mass lesions. The third VE case was associated with numerous microhemorrhages in keeping with cerebral amyloid angiopathy‐related inflammation or Aβ‐related angiitis. The final VE case demonstrated localized sulcal fluid‐attenuated inversion recovery imaging hyperintensity. No VE was detected in cohort 3 by readers blinded to patient baseline status.ConclusionsVE seems to be rare at baseline in patients with AD in clinical trials, 2 of 2762 associated with AD. Additional cohorts should be evaluated to support these findings.

Abstract Session 1 of the 2009 Workshop of the Society for Hematopathology/European Association of Haematopathology, Cleveland, OH, focused on plasma cell neoplasms. This report summarizes the salient diagnostic, clinical, and genetic features of plasma cell myeloma (PCM) and related neoplasms. Based on the cases submitted to the workshop, we highlight common diagnostic issues and unusual manifestations of plasma cell neoplasms, such as t(11;14)+ PCM, plasma cell leukemia, and nonsecretory plasmacytoma, as well as plasmablastic transformation of PCM. Additional issues repeatedly raised at the workshop included the differential diagnosis of extramedullary dissemination of PCM vs primary extramedullary plasmacytoma and plasmablastic lymphoma; systemic plasma cell neoplasms in immunocompromised people; and Epstein-Barr virus–associated plasma cell neoplasms. Difficult cases with borderline features presented by submitters emphasized the necessity of integrating clinical, immunophenotypic, and genetic features for appropriate classification of these disorders.

Abstract Purpose: Cell-based approaches were used to identify genetic markers predictive of patients' risk for poor response prior to chemotherapy. Experimental Design: We conducted genome-wide association studies (GWAS) to identify single-nucleotide polymorphisms (SNP) associated with cellular sensitivity to carboplatin through their effects on mRNA expression using International HapMap lymphoblastoid cell lines (LCL) and replicated them in additional LCLs. SNPs passing both stages of the cell-based study were tested for association with progression-free survival (PFS) in patients. Phase 1 validation was based on 377 ovarian cancer patients receiving at least four cycles of carboplatin and paclitaxel from the Australian Ovarian Cancer Study (AOCS). Positive associations were then assessed in phase 2 validation analysis of 1,326 patients from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas. Results: In the initial GWAS, 342 SNPs were associated with carboplatin-induced cytotoxicity, of which 18 unique SNPs were retained after assessing their association with gene expression. One SNP (rs1649942) was replicated in an independent LCL set (Bonferroni adjusted P < 0.05). It was found to be significantly associated with decreased PFS in phase 1 AOCS patients (Pper-allele = 2 × 10−2), with a stronger effect in the subset of women with optimally debulked tumors (Pper-allele = 4 × 10−3). rs1649942 was also associated with poorer overall survival in women with optimally debulked tumors (Pper-allele = 9 × 10−3). However, this SNP was not significant in phase 2 validation analysis with patients from numerous cohorts. Conclusion: This study shows the potential of cell-based, genome-wide approaches to identify germline predictors of treatment outcome and highlights the need for extensive validation in patients to assess their clinical effect. Clin Cancer Res; 17(16); 5490–500. ©2011 AACR.