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      Continued improvement in survival of acute myeloid leukemia patients: an application of the loss in expectation of life

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          Abstract

          We evaluated temporal trends in survival of Swedish acute myeloid leukemia (AML) patients diagnosed between 1973 and 2011 using relative survival ratios (RSRs) and a measure called the loss in expectation of life (LEL). RSRs increased most for patients <60 years at diagnosis during the first calendar periods, but between 1997–2005 and 2006–2011 the most pronounced increase was for those aged 61–70 years at diagnosis; RSR changed from 0.16 (95% confidence interval (CI): 0.13–0.19) to 0.28 (95% CI: 0.23–0.33), respectively. The LEL for males aged 35 years at diagnosis was 41.0 (95% CI: 40.1–41.8) years in 1975 and 19.5 (95% CI: 16.4–22.5) years in 2011. For males aged 65 years, the corresponding figures were 13.8 (95% CI: 13.7–14.0) and 12.0 (95% CI: 11.3–12.8). Conditional LEL estimates suggested that patients who survive 5 years postdiagnosis have shorter remaining lifespan than the general population. The proportion of expected life lost (PELL) suggested that male 65-year-old patients lost 75% of their life expectancy in 2005 and 66% if they were diagnosed in 2011. Survival continued to increase to 2011, with larger improvements in those aged 61–70 years at diagnosis. The LEL and PELL are intuitive measures that may be useful in communicating survival statistics to patients, clinicians and health-care providers.

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          Therapeutic advances in acute myeloid leukemia.

          The choice of treatment approach and outcome in acute myeloid leukemia (AML) depends on the age of the patient. In younger patients, arbitrarily defined as being younger than 60 years, 70% to 80% enter complete disease remission with several anthracycline-based chemotherapy combinations. Consolidation with high-dose cytarabine or stem-cell transplantation in high-risk patients will restrict overall relapse to approximately 50%. A number of demographic features can predict the outcome of treatment including cytogenetics and an increasing list of molecular features (ie, FLT3, NPM1, MLL, WT1, CEBPalpha, EVI1). These are increasingly being used to direct postinduction therapy, but they are also molecular targets for a new generation of small molecule inhibitors that are in early development; however, randomized data have yet to emerge. In older patients who comprise the majority, which will increase with demographic change, the initial clinical decision to be made is whether the patient should receive an intensive or nonintensive approach. If the same anthracycline/cytarabine-based approach is deployed, the remission rate will be around 50%, but the risk of subsequent relapse is approximately 85% at 3 years. This difference from younger patients is explained partly by the ability of patients to tolerate effective therapy, and also the aggregation of several poor risk factors compared with the young. There remains a substantial proportion of patients older than 60 years who do not receive intensive chemotherapy. Their survival is approximately 4 months, but there is considerable interest in developing new treatments for this patient group, including novel nucleoside analogs and several other agents.
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            The relative survival rate: a statistical methodology.

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              High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study.

              Half the patients with acute myeloid leukemia (AML) who achieve complete remission (CR), ultimately relapse. Residual treatment-surviving leukemia is considered responsible for the outgrowth of AML. In many retrospective studies, detection of minimal residual disease (MRD) has been shown to enable identification of these poor-outcome patients by showing its independent prognostic impact. Most studies focus on molecular markers or analyze data in retrospect. This study establishes the value of immunophenotypically assessed MRD in the context of a multicenter clinical trial in adult AML with sample collection and analysis performed in a few specialized centers. In adults (younger than age 60 years) with AML enrolled onto the Dutch-Belgian Hemato-Oncology Cooperative Group/Swiss Group for Clinical Cancer Research Acute Myeloid Leukemia 42A study, MRD was evaluated in bone marrow samples in CR (164 after induction cycle 1, 183 after cycle 2, 124 after consolidation therapy). After all courses of therapy, low MRD values distinguished patients with relatively favorable outcome from those with high relapse rate and adverse relapse-free and overall survival. In the whole patient group and in the subgroup with intermediate-risk cytogenetics, MRD was an independent prognostic factor. Multivariate analysis after cycle 2, when decisions about consolidation treatment have to be made, confirmed that high MRD values (> 0.1% of WBC) were associated with a higher risk of relapse after adjustment for consolidation treatment time-dependent covariate risk score and early or later CR. In future treatment studies, risk stratification should be based not only on risk estimation assessed at diagnosis but also on MRD as a therapy-dependent prognostic factor.
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                Author and article information

                Journal
                Blood Cancer J
                Blood Cancer J
                Blood Cancer Journal
                Nature Publishing Group
                2044-5385
                February 2016
                05 February 2016
                1 February 2016
                : 6
                : 2
                : e390
                Affiliations
                [1 ]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm, Sweden
                [2 ]Department of Medicine, Division of Hematology, Karolinska University Hospital Solna and Karolinska Institutet , Stockholm, Sweden
                [3 ]Department of Health Sciences, University of Leicester , Leicester, UK
                Author notes
                [* ]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , PO Box 281, Stockholm SE-171 77, Sweden. E-mail: hannah.bower@ 123456ki.se
                [4]

                Both senior authors and contributed equally to this manuscript.

                Article
                bcj20163
                10.1038/bcj.2016.3
                4771966
                26849011
                c67ace2f-fa8f-43ac-9cf9-1c3fad60cf48
                Copyright © 2016 Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 30 November 2015
                : 17 December 2015
                Categories
                Original Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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