Acute myeloid leukemias (AMLs) are infrequent, yet highly malignant neoplasms responsible for a large number of cancer-related deaths. The incidence has been near stable over the last years. It continuously shows 2 peaks in occurrence in early childhood and later adulthood. With an incidence of 3.7 per 100,000 persons and an age-dependent mortality of 2.7 to nearly 18 per 100,000 persons, there is a rising awareness in the Western world of AML's special attributes resulting from an ever-aging population. To objectively describe epidemiologic data on this patient population, recent publications were evaluated to make transparent the current trends and facts. A review of the literature is presented, reflecting highlights of current research with respect to AML etiology. To estimate outcome and discuss informed treatment decisions with AML patients of different age groups and different biologic risk categories, it is mandatory to consider that the outcome results reported in clinical trials were until now heavily biased toward younger patients, whereas the overall dismal prognosis documented in population-based studies most likely reflects the exclusion of older patients from aggressive treatment. The etiology for most cases of AML is unclear, but a growing knowledge concerning leukemogenenic agents within chemotherapy regimens for other malignancies is already available. This includes specific associations of the most frequent balanced translocations in AML, including the ''good-risk'' abnormalities comprised by the core binding factor leukemias (i.e., AML with the translocation (8;21) and inversion of chromosome 16, and acute promyelocytic leukemia with the translocation (15;17)). In contrast to these genetic alterations, epigenetic lesions, e.g., promoter silencing by hypermethylation of the p15/INK4b and other genes, are increasingly recognized as important in the pathogenesis of AML.

The online version of this article has a Supplementary Appendix. BackgroundThe treatment of acute myeloid leukemia of older, medically non-fit patients still poses a highly unmet clinical need, and only few large, prospective studies have been performed in this setting. Given the established activity of hypomethylating agents such as 5-aza-2'-deoxycytidine (decitabine) in myelodysplastic syndromes and acute myeloid leukemia with 20-30% bone marrow blasts, we investigated whether this drug is also active in patients with more than 30% blasts. Design and MethodsTo evaluate the efficacy and toxicity of decitabine in patients over 60 years old with untreated acute myeloid leukemia ineligible for induction chemotherapy, 227 patients (median age, 72 years), many with comorbidities, adverse cytogenetics and/or preceding myelodysplastic syndrome were treated with this hypomethylating agent. During the initial decitabine treatment (135 mg/m 2 total dose infused intravenously over 72 hours every 6 weeks), a median of two cycles was administered (range, 1-4). All-trans retinoic acid was administered to 100 patients during course 2. Fifty-two patients who completed four cycles of treatment subsequently received a median of five maintenance courses (range, 1-19) with a lower dose of decitabine (20 mg/m 2 ) infused over 1 hour on 3 consecutive days every 4-6 weeks. ResultsThe complete and partial remission rate was 26%, 95% CI (20%, 32%), and an antileukemic effect was noted in 26% of patients. Response rates did not differ between patients with or without adverse cytogenetics; patients with monosomal karyotypes also responded. The median overall survival from the start of decitabine treatment was 5.5 months (range, 0-57.5+) and the 1-year survival rate was 28%, 95%CI (22%,34%). Toxicities were predominantly hematologic. ConclusionsDecitabine is well tolerated by older, medically non-fit patients with acute myeloid leukemia; myelosuppression is the major toxicity. The response rate and overall survival were not adversely influenced by poor-risk cytogenetics or myelodysplastic syndrome. Because of these encouraging results, randomized studies evaluating single-agent decitabine versus conventional treatment are warranted. The study is registered with the German Clinical Trials Registry, number DRKS00000069. chemotherapy. Haematologica 2012;97(3):393-401. doi:10.3324/haematol.2011 This is an open-access paper.A multicenter phase II trial of decitabine as first-line treatment for older patients with acute myeloid leukemia judged unfit for induction chemotherapy

Myelodysplastic syndromes and acute myeloid leukemia exemplify the complexity of treatment allocation in older patients as options range from best supportive care, non-intensive treatment (e.g. hypomethylating agents) to intensive chemotherapy/hematopoietic cell transplantation. Novel metrics for non-disease variables are urgently needed to help define the best treatment for each older patient. We investigated the feasibility and prognostic value of geriatric/quality of life assessments aside from established disease-specific variables in 195 patients aged 60 years or over with myelodysplastic syndromes/acute myeloid leukemia. These patients were grouped according to treatment intensity and assessed. Assessment consisted of eight instruments evaluating activities of daily living, depression, mental functioning, mobility, comorbidities, Karnofsky Index and quality of life. Patients with a median age of 71 years (range 60-87 years) with myelodysplastic syndromes (n=63) or acute myeloid leukemia (n=132) were treated either with best supportive care (n=47), hypomethylating agents (n=73) or intensive chemotherapy/hematopoietic cell transplantation (n=75). After selection of variables, pathological activities of daily living and quality of life/fatigue remained highly predictive for overall survival in the entire patient group beyond disease-related risk factors adverse cytogenetics and blast count of 20% or over. In 107 patients treated non-intensively activities of daily living of less than 100 (hazard ratio, HR 2.94), Karnofsky Index below 80 (HR 2.34) and quality of life/'fatigue' of 50 or over (HR 1.77) were significant prognosticators. Summation of adverse features revealed a high risk of death (HR 9.36). In-depth evaluation of older patients prior to individual treatment allocation is feasible and provides additional information to standard assessment. Patients aged 60 years or over with newly diagnosed myelodysplastic syndromes/acute myeloid leukemia and impairments in activities of daily living, Karnofsky Index below 80%, quality of life/'fatigue' of 50 or over, are likely to have poor outcomes.Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome