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      Low-intensity regimens versus standard-intensity induction strategies in acute myeloid leukemia

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          Abstract

          Treatment options for elderly patients with acute myeloid leukemia (AML) remain limited. In this age group, AML is frequently associated with poor-risk features, while patients’ present comorbidities and reduced functional reserves. As such, intensive chemotherapy (ICT) is frequently too toxic or ineffective in elderly patients and is restricted to a select minority, though it is standard therapy for the youngest and fittest patients or for those belonging to either the favorable or intermediate-risk groups. The use of hypomethylating agents represent an effective alternative for patients who are unfit for ICT, yet the results remain unsatisfactory. In recent years, prognostic scores were developed that include geriatric assessment tools and improved risk-stratification. In addition, several effective new drugs have emerged. The combination of these drugs with hypomethylating agents or low-dose cytarabine has produced encouraging preliminary results that may change standard practices and offer an alternative to the dilemma of ICT versus low-intensity therapies.

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          Most cited references51

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          Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study.

          Elderly patients (aged ≥65 years) with acute myeloid leukaemia have poor outcomes and no effective standard-of-care therapy exists. Treatment with hypomethylating agents such as azacitidine and decitabine is common, but responses are modest and typically short-lived. The oral anti-apoptotic B-cell lymphoma 2 protein inhibitor, venetoclax, has shown promising single-agent activity in patients with relapsed or refractory acute myeloid leukaemia and preclinical data suggested synergy between hypomethylating agents and venetoclax, which led to this combination phase 1b study.
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            High-dose daunorubicin in older patients with acute myeloid leukemia.

            A complete remission is essential for prolonging survival in patients with acute myeloid leukemia (AML). Daunorubicin is a cornerstone of the induction regimen, but the optimal dose is unknown. In older patients, it is usual to give daunorubicin at a dose of 45 to 50 mg per square meter of body-surface area. Patients in whom AML or high-risk refractory anemia had been newly diagnosed and who were 60 to 83 years of age (median, 67) were randomly assigned to receive cytarabine, at a dose of 200 mg per square meter by continuous infusion for 7 days, plus daunorubicin for 3 days, either at the conventional dose of 45 mg per square meter (411 patients) or at an escalated dose of 90 mg per square meter (402 patients); this treatment was followed by a second cycle of cytarabine at a dose of 1000 mg per square meter every 12 hours [DOSAGE ERROR CORRECTED] for 6 days. The primary end point was event-free survival. The complete remission rates were 64% in the group that received the escalated dose of daunorubicin and 54% in the group that received the conventional dose (P=0.002); the rates of remission after the first cycle of induction treatment were 52% and 35%, respectively (P<0.001). There was no significant difference between the two groups in the incidence of hematologic toxic effects, 30-day mortality (11% and 12% in the two groups, respectively), or the incidence of moderate, severe, or life-threatening adverse events (P=0.08). Survival end points in the two groups did not differ significantly overall, but patients in the escalated-treatment group who were 60 to 65 years of age, as compared with the patients in the same age group who received the conventional dose, had higher rates of complete remission (73% vs. 51%), event-free survival (29% vs. 14%), and overall survival (38% vs. 23%). In patients with AML who are older than 60 years of age, escalation of the dose of daunorubicin to twice the conventional dose, with the entire dose administered in the first induction cycle, effects a more rapid response and a higher response rate than does the conventional dose, without additional toxic effects. (Current Controlled Trials number, ISRCTN77039377; and Netherlands National Trial Register number, NTR212.) 2009 Massachusetts Medical Society
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              Acute Myeloid Leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology

              Acute myeloid leukemia (AML) is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. Recent advances have resulted in an expansion of treatment options for AML, especially concerning targeted therapies and low-intensity regimens. This portion of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML focuses on the management of AML and provides recommendations on the workup, diagnostic evaluation and treatment options for younger (age <60 years) and older (age ≥60 years) adult patients.
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                Author and article information

                Contributors
                Journal
                Ther Adv Hematol
                Ther Adv Hematol
                TAH
                sptah
                Therapeutic Advances in Hematology
                SAGE Publications (Sage UK: London, England )
                2040-6207
                2040-6215
                18 March 2020
                2020
                : 11
                : 2040620720913010
                Affiliations
                [1-2040620720913010]Institut Paoli-Calmettes, 232 Boulevard de Sainte Marguerite, Marseille, 13009, France
                [2-2040620720913010]Univ-med Aix Marseille, IPC Department of Hematology and CRCM, Marseille, France
                Author notes
                Author information
                https://orcid.org/0000-0001-7027-040X
                Article
                10.1177_2040620720913010
                10.1177/2040620720913010
                7081460
                32215195
                b190ca7b-1ad0-4df8-8507-7afc217f788c
                © The Author(s), 2020

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 23 July 2019
                : 12 February 2020
                Categories
                Review
                Custom metadata
                January-December 2020
                ts1

                Hematology
                acute myeloid leukemia,elderly,hypomethylating agents,low-dose cytarabine,intensive chemotherapy

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