br Prognosis The management of AML in the elderly
Prognosis The management of AML in the elderly patient presents a significant challenge for hematologists. Careful evaluation of both patient and disease is required in each individual case to make optimal management decisions, and maximize the benefit to the patient. Apart from the extremely old patients, chronological age per se is particularly unreliable in identifying patients who will not tolerate intensive regimens. As stated in the introduction, AML in the older adult shows some biological differences with AML in the young. As far as prognostic factors are concerned (see Table 2), the vast majority are the same, but their relative proportion is different. The data from MRC/LRF, based on more than two thousand patients included in clinical trials in UK, showed that age, performance status, white blood cell count, cytogenetics, and type of AML (de novo vs. secondary) are the most relevant prognostic factors . Recent analysis of population-derived data from Sweden  included outcomes from over 3000 adult AML patients, of which 26% had secondary AML. Analysis of prognostic factors found that secondary AML significantly impacted survival in younger patients but, in older patients, it did not emerge as an independent poor prognostic factor, suggesting that secondary AML lacks the prognostic impact in this caged compounds previously attributed by the MRC/LRF . Flow cytometry has attained a central role in the diagnosis of AML and recent data have shown that the degree of phenotypic maturity determined by this technique can also deliver important prognostic information in the elders . These phenotypes can predict both CR rates and survival, suggesting that they reflect intrinsic resistance to treatment. The prognostic weight of minimal residual disease assessed by flow cytometry seems comparatively higher in the elders than in the young . By contrast, the relative impact of molecular findings in the elderly is poorly defined, probably as a consequence of a less intensive research in this population. At present time, the impact of the associations appears to be in general the same than in the young, despite the fact that their relative weight may be lower . Interestingly, in some particular cases, such as DNMT3A codon R882 mutations , the behavior is opposite. Finally, the best-defined prognostic factors come from selected cohorts of patients participating in clinical trials, something that might have hidden other patient-derived prognostic factors. In this sense, comorbidity [5,30], polypharmacy , physical function and cognition [32,33], as well as fatigue , appear to be also relevant for prognosis, since they impact on patient\'s ability to withstand the insult of chemotherapy and/or hematopoietic cell transplantation (HCT). Among specific comorbidities, previous cerebrovascular, renal, liver, psychiatric and rheumatological diseases have been particularly associated with increased risk of death . As regards comorbidity scores, the Charlson comorbidity index  and the HCT comorbidity index (HCT-CI)  have been shown to predict overall survival in elderly AML.
Treatment options Life expectancy in AML not only depends on the disease itself, but also on usual risk factors for mortality in the general population. Nevertheless, the tremendous impact of AML on the short term (conferring a very high relative mortality) overrides any other consideration as regards the eventual need for specific therapy. Thus, if the patient does not receive specific treatment, his/her life expectancy will probably be only a few months since diagnosis, although low-blast count AML might have a slower evolution . Nowadays, only 40% of the elderly population receive specific AML therapy within the first 3 months from diagnosis in the US, according to recent data from SEER-Medicare Database, highlighting that there is much room for improvement in this field .