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      Trends in survival of chronic lymphocytic leukemia patients in Germany and the USA in the first decade of the twenty-first century

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          Abstract

          Background

          Recent population-based studies in the United States of America (USA) and other countries have shown improvements in survival for patients with chronic lymphocytic leukemia (CLL) diagnosed in the early twenty-first century. Here, we examine the survival for patients diagnosed with CLL in Germany in 1997–2011.

          Methods

          Data were extracted from 12 cancer registries in Germany and compared to the data from the USA. Period analysis was used to estimate 5- and 10-year relative survival (RS).

          Results

          Five- and 10-year RS estimates in 2009–2011 of 80.2 and 59.5 %, respectively, in Germany and 82.4 and 64.7 %, respectively, in the USA were observed. Overall, 5-year RS increased significantly in Germany and the difference compared to the survival in the USA which slightly decreased between 2003–2005 and 2009–2011. However, age-specific analyses showed persistently higher survival for all ages except for 15–44 in the USA. In general, survival decreased with age, but the age-related disparity was small for patients younger than 75. In both countries, 5-year RS was >80 % for patients less than 75 years of age but <70 % for those age 75+.

          Conclusions

          Overall, 5-year survival for patients with CLL is good, but 10-year survival is significantly lower, and survival was much lower for those age 75+. Major differences in survival between countries were not observed. Further research into ways to increase survival for older CLL patients are needed to reduce the persistent large age-related survival disparity.

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          Most cited references31

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          Relation of Gene Expression Phenotype to Immunoglobulin Mutation Genotype in B Cell Chronic Lymphocytic Leukemia

          The most common human leukemia is B cell chronic lymphocytic leukemia (CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression “signature,” irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin. Nonetheless, the expression of hundreds of other genes correlated with the Ig mutational status, including many genes that are modulated in expression during mitogenic B cell receptor signaling. These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease.
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            Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia.

            Fludarabine is an effective treatment for chronic lymphocytic leukemia that does not respond to initial treatment with chlorambucil. We compared the efficacy of fludarabine with that of chlorambucil in the primary treatment of chronic lymphocytic leukemia. Between 1990 and 1994, we randomly assigned 509 previously untreated patients with chronic lymphocytic leukemia to one of the following treatments: fludarabine (25 mg per square meter of body-surface area, administered intravenously daily for 5 days every 28 days), chlorambucil (40 mg per square meter, given orally every 28 days), or fludarabine (20 mg per square meter per day for 5 days every 28 days) plus chlorambucil (20 mg per square meter every 28 days). Patients with an additional response at each monthly evaluation continued to receive the assigned treatment for a maximum of 12 cycles. Assignment of patients to the fludarabine-plus-chlorambucil group was stopped when a planned interim analysis revealed excessive toxicity and a response rate that was not better than the rate with fludarabine alone. Among the other two groups, the response rate was significantly higher for fludarabine alone than for chlorambucil alone. Among 170 patients treated with fludarabine, 20 percent had a complete remission, and 43 percent had a partial remission. The corresponding values for 181 patients treated with chlorambucil were 4 percent and 33 percent (P< 0.001 for both comparisons). The median duration of remission and the median progression-free survival in the fludarabine group were 25 months and 20 months, respectively, whereas both values were 14 months in the chlorambucil group (P<0.001 for both comparisons). The median overall survival among patients treated with fludarabine was 66 months, which was not significantly different from the overall survival in the other two groups (56 months with chlorambucil and 55 months with combined treatment). Severe infections and neutropenia were more frequent with fludarabine than with chlorambucil (P=0.08), although, overall, toxic effects were tolerable with the two single-drug regimens. When used as the initial treatment for chronic lymphocytic leukemia, fludarabine yields higher response rates and a longer duration of remission and progression-free survival than chlorambucil.
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              Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group.

              We investigated the safety and efficacy of bendamustine and rituximab (BR) in previously untreated patients with chronic lymphocytic leukemia (CLL). In all, 117 patients, age 34 to 78 years, 46.2% of patients at Binet stage C, and 25.6% of patients age 70 years or older received BR chemoimmunotherapy for first-line treatment of CLL. Bendamustine was administered at a dose of 90 mg/m(2) on days 1 and 2 combined with 375 mg/m(2) rituximab on day 0 of the first course and 500 mg/m(2) on day 1 during subsequent courses for up to six courses. Overall response rate was 88.0% (95% CI, 80.7% to 100.0%) with a complete response rate of 23.1% and a partial response rate of 64.9%. Ninety percent of patients with del(11q), 94.7% with trisomy 12, 37.5% with del(17p), and 89.4% with unmutated IGHV status responded to treatment. After a median observation time of 27.0 months, median event-free survival was 33.9 months, and 90.5% of patients were alive. Grade 3 or 4 severe infections occurred in 7.7% of patients. Grade 3 or 4 adverse events for neutropenia, thrombocytopenia, and anemia were documented in 19.7%, 22.2%, and 19.7% of patients, respectively. Chemoimmunotherapy with BR is effective and safe in patients with previously untreated CLL.
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                Author and article information

                Contributors
                +49-6221-42-1350 , pultedi@gmail.com
                Journal
                J Hematol Oncol
                J Hematol Oncol
                Journal of Hematology & Oncology
                BioMed Central (London )
                1756-8722
                22 March 2016
                22 March 2016
                2016
                : 9
                : 28
                Affiliations
                [ ]Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69121 Heidelberg, Germany
                [ ]Cardeza Foundation and Division of Hematology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA USA
                [ ]Bremen Cancer Registry, Leibniz-Institute for Prevention Research and Epidemiology—BIPS, Bremen, Germany
                [ ]Saarland Cancer Registry, Saarbrücken, Germany
                [ ]Hamburg Cancer Registry, Authority for Health and Consumer Protection, Hamburg, Germany
                [ ]Cancer Registry of Rhineland-Palatinate, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
                [ ]Cancer Registry of Schleswig-Holstein, Lübeck, Germany
                [ ]Division of Preventative Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
                [ ]German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
                Article
                257
                10.1186/s13045-016-0257-2
                4802710
                27000264
                ecea8868-d1e2-4863-b8f8-d37a4c8b8a2c
                © Pulte et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 1 February 2016
                : 11 March 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100005972, Deutsche Krebshilfe;
                Award ID: 108257
                Funded by: FundRef http://dx.doi.org/10.13039/100008658, Deutsches Krebsforschungszentrum;
                Award ID: N/A
                Award Recipient :
                Categories
                Research
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                © The Author(s) 2016

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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