BackgroundClinical management of chronic lymphocytic leukemia patients has changed considerably over the last years, reflected in an increased use of prognostic markers, new therapeutic agents and procedures, and supportive care measures. However, to date, clinical trials have not shown a survival benefit. Design and MethodsUsing population-based data from Sweden, we assessed variations in survival among all chronic lymphocytic leukemia patients (n=11,179) reported from 1973-2003. Relative survival ratios were computed as measures of patient survival. ResultsOverall we found significantly improved (p<0.0001) 5-, 10-, and 20-year relative survival ratio for the entire cohort during the study period. Improved 5-and 10-year relative survival ratio was found for all age-groups (p<0.0001) and both sexes. Compared to females, however, males had a significantly inferior survival in all age groups and calendar periods (p<0.0001). Younger chronic lymphocytic leukemia patients had a superior survival compared to older chronic lymphocytic leukemia patients, in all calendar periods (p<0.0001). Five-year relative survival ratio has not improved in the youngest chronic lymphocytic leukemia patients since the 1980s; however, older patients have had a continuous improvement in 5 year-relative survival ratio. ConclusionsThe observed improvements are likely due to improved therapeutic developments and supportive care. Our findings suggest that elderly chronic lymphocytic leukemia patients might benefit more from the recently introduced drugs in chronic lymphocytic leukemia. Future clinical trials are needed to better define underlying mechanisms of observed heterogeneity in chronic lymphocytic leukemia survival by age and sex, and evaluate the role of newer chronic lymphocytic leukemia therapy in the elderly.Key words: chronic lymphocytic leukemia, prognosis, survival, sex, older age, population-based.Citation: Kristinsson SY, Dickman PW, Wilson WH, Caporaso N, Björkholm M, and Landgren O. Improved survival in chronic lymphocytic leukemia in the past decade: a population-based study including 11,179 patients diagnosed between 1973-2003 in Sweden. Haematologica 200994:1259-1265. doi:10.3324/haematol.2009

Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites.

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An evaluation of the reproducibility and accuracy of the NMR human blood test for cancer described by Fossel, E. T., Carr, J. M. and McDonagh, J., (New England Journal of Medicine 315, 1369-1376) in 1986 has been conducted jointly at the National Cancer Institute-Frederick Cancer Research Facility, Frederick, MD (NCI-FCRF) and the National Research Council, Ottawa, Canada (NRC). The influences on the test of the following were studied: (a) subject fasting; (b) sample collection, storage and handling; (c) use of plasma or serum; (d) variations of test results from the same individual with time; (e) NMR observation parameters including field strength and temperature; and (f) variations in obtaining the Fossel Index (FI) (a number defined by Fossel and co-workers as the average of the widths at half height of the regions in the NMR spectrum of human plasma at 1.3 and 0.88 ppm) by different people from the same plotted spectrum. This test was found to be reproducible but not accurate for screening a general asymptomatic population. The accuracy is defined in terms of the sensitivity, specificity, and predictive values of the test. The accuracy of the test results from our laboratories is compared with the accuracies from other laboratories including Fossel's. The correlation of the Fossel Index with total triglyceride content in the serum has been confirmed by analysing blood components using the following technologies: KBr density gradient centrifugation, high resolution agarose gel electrophoresis, high performance gel permeation chromatography, and chemical analysis.