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      Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States

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          Abstract

          Over half of patients diagnosed with acute myeloid leukemia (AML) are 65 years or older. We examined patient characteristics, treatment patterns, and survival among elderly patients in routine clinical practice. We utilized a retrospective cohort analysis of first primary AML patients in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were diagnosed between January 1, 2000 and December 31, 2009, >66 years, and continuously enrolled in Medicare Part A and B in the year prior to diagnosis. Kaplan-Meier curves and Cox proportional hazards regression assessed overall survival by treatment. There were 3327 (40 %) patients who received chemotherapy within 3 months of diagnosis. Treated patients were more likely younger, male, and married, and less likely to have secondary AML and poor performance indicators and comorbidity score compared to untreated patients. In multivariate survival analysis, treated patients exhibited a significant 33 % lower risk of death compared to untreated patients. Significant survival benefits were noted with receipt of intensive and hypomethylating agent (HMA) therapies compared to no therapy. A survival benefit with allogeneic hematopoietic stem cell transplantation was seen in younger Medicare patients. This real-world study showed that about 60 % of elderly AML patients remain untreated following diagnosis. Use of anti-leukemic therapy was associated with a significant survival benefit in this elderly cohort.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s00277-015-2351-x) contains supplementary material, which is available to authorized users.

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          Marital status and survival in patients with cancer.

          To examine the impact of marital status on stage at diagnosis, use of definitive therapy, and cancer-specific mortality among each of the 10 leading causes of cancer-related death in the United States.
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            Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia.

            In a phase III randomized trial, azacitidine significantly prolonged overall survival (OS) compared with conventional care regimens (CCRs) in patients with intermediate-2- and high-risk myelodysplastic syndromes. Approximately one third of these patients were classified as having acute myeloid leukemia (AML) under current WHO criteria. This analysis compared the effects of azacitidine versus CCR on OS in this subgroup. Patients were randomly assigned to receive subcutaneous azacitidine 75 mg/m(2)/d or CCR (best supportive care [BSC] only, low-dose cytarabine (LDAC), or intensive chemotherapy [IC]). Of the 113 elderly patients (median age, 70 years) randomly assigned to receive azacitidine (n = 55) or CCR (n = 58; 47% BSC, 34% LDAC, 19% IC), 86% were considered unfit for IC. At a median follow-up of 20.1 months, median OS for azacitidine-treated patients was 24.5 months compared with 16.0 months for CCR-treated patients (hazard ratio = 0.47; 95% CI, 0.28 to 0.79; P = .005), and 2-year OS rates were 50% and 16%, respectively (P = .001). Two-year OS rates were higher with azacitidine versus CCR in patients considered unfit for IC (P = .0003). Azacitidine was associated with fewer total days in hospital (P < .0001) than CCR. In older adult patients with low marrow blast count (20% to 30%) WHO-defined AML, azacitidine significantly prolongs OS and significantly improves several patient morbidity measures compared with CCR.
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              Results of multivariable logistic regression, propensity matching, propensity adjustment, and propensity-based weighting under conditions of nonuniform effect.

              Observational studies often provide the only available information about treatment effects. Control of confounding, however, remains challenging. The authors compared five methods for evaluating the effect of tissue plasminogen activator on death among 6,269 ischemic stroke patients registered in a German stroke registry: multivariable logistic regression, propensity score-matched analysis, regression adjustment with the propensity score, and two propensity score-based weighted methods-one estimating the treatment effect in the entire study population (inverse-probability-of-treatment weights), another in the treated population (standardized-mortality-ratio weights). Between 2000 and 2001, 212 patients received tissue plasminogen activator. The crude odds ratio between tissue plasminogen activator and death was 3.35 (95% confidence interval: 2.28, 4.91). The adjusted odds ratio depended strongly on the adjustment method, ranging from 1.11 (95% confidence interval: 0.67, 1.84) for the standardized-mortality-ratio weighted to 10.77 (95% confidence interval: 2.47, 47.04) for the inverse-probability-of-treatment-weighted analysis. For treated patients with a low propensity score, risks of dying were high. Exclusion of patients with a propensity score of <5% yielded comparable odds ratios of approximately 1 for all methods. High levels of nonuniform treatment effect render summary estimates very sensitive to the weighting system explicit or implicit in an adjustment technique. Researchers need to be clear about the population for which an overall treatment estimate is most suitable.
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                Author and article information

                Contributors
                916-297-0979 , sacha@qdresearch.com
                Journal
                Ann Hematol
                Ann. Hematol
                Annals of Hematology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0939-5555
                1432-0584
                20 March 2015
                20 March 2015
                2015
                : 94
                : 7
                : 1127-1138
                Affiliations
                [ ]Stanford University, 875 Blake Wilbur Dr, Stanford, CA USA
                [ ]Q.D. Research, Inc., 8777 Auburn Folsom Road C501, Granite Bay, CA 95746 USA
                [ ]Genentech, Inc., 1 DNA Way, South San Francisco, CA USA
                [ ]University of California, San Francisco, San Francisco, CA USA
                Article
                2351
                10.1007/s00277-015-2351-x
                4432101
                25791241
                88071564-381a-453d-a0ac-d4543963d1d9
                © The Author(s) 2015

                Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 2 January 2015
                : 4 March 2015
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2015

                Hematology
                acute myeloid leukemia,elderly,treatment,chemotherapy,stem cell transplantation,survival
                Hematology
                acute myeloid leukemia, elderly, treatment, chemotherapy, stem cell transplantation, survival

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