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  • Introduction Acute myeloid leukemia AML is

    2019-05-05

    Introduction Acute myeloid leukemia (AML) is a rare disease afflicting annually 3–4 persons per 100,000 individuals. With a median age at diagnosis of 67 years, this disease is far more common in the elderly [1]. In this age group, AML has a particularly dismal outcome with less than 5% of the patients being alive 5 years after the diagnosis, as compared to 40% in the young [2,3]. Considering that individuals aged 65 in the Western world are expected to survive approximately another 20 years, and even those aged 80 three additional years [4], AML has a devastating impact on the survival of this age group. The reasons for the poor outcomes in the older adults are both patient- and disease-related. Advanced age is often accompanied by frailty and comorbidities, which have an important impact on the tolerance these patients have to intensive treatment modalities [5]. In addition, the lower rates of complete remission (CR) in the elderly (40–50% vs 60–70% in the young) [3] and the short duration seen in those who are eligible for treatment [5], point towards a different disease biology in this age group. From a clinical viewpoint, it is far more frequent for elderly patients to have received previous cytotoxic treatment or radiotherapy or to have antecedent hematologic diseases, such as myelodysplastic (MDS) or myeloproliferative neoplasms [5]. In addition to po1 these clinical features, the cytogenetic profile of elderly patients with AML also differs from that of younger patients, presenting a greater incidence of multiple chromosomal abnormalities [6]. The introduction of new potent sequencing technologies has shed considerable light on the molecular mechanisms of AML pathophysiology, and further reinforced the observation that AML in the elderly is biologically distinct. Thus, mutation screening has identified mutations in genes coding for epigenetic regulators, such as TET2, DMNT3A, IDH1/2, ASXL1 and EZH2, kinases and po1 regulators, such as TP53, NPM1 and FLT3 and transcription factors, such as RUNX1 and CEBPA [7], and showed that the cytogenetic and mutational profile of AML in the older adults patients is significantly different from that of younger patients [8]. The methylation patterns seen in them resemble more closely those seen in MDS [9]. These unique features of AML in the elderly population urge a fresh approach to these patients.
    Geriatric assessment Older adults frequently have an advanced biological age. This not a constant feature and a number of them keep fit and healthy until late in their lives. Nevertheless, the opportunity to develop several diseases, as well as to acquire a low functional reserve, increases with chronological age and any experienced malignant hematologist recognizes that some elderly AML patients may be unable to withstand intensive chemotherapy and allogeneic hemopoietic cell transplantation. An excruciating clinical problem is how to predict with confidence such a situation when confronting an apparently fit/unfit individual patient. In this situation, a comprehensive geriatric assessment (CGA) is the appropriate answer and the National Comprehensive Cancer Network has issued specific guidelines to help the physician in the care of older adults with cancer [10]. However, CGA is somehow complex and not always readily available. Some screening tools (e.g. VES13 or G8) have been developed to decide which patients deserve a CGA in order to optimize resources [11,12]. Despite the fact that they predict survival in hematological patients (eg. G8 score up to 14 score points seems a bad prognostic factor), their sensitivity and specificity as compared to the gold standard (i.e. CGA) is not optimal [13,14] and a simplified geriatric assessment approach is much needed and now actively pursued (see the next section). Our suggestion for this purpose, based on the approach of Klepin et al. [15,16], is shown in Table 1 and requires that the clinical team becomes familiar with some additional clinical tools beyond performance status and comorbidity scores [17,18], such us the Short Physical Performance Battery [19], or the more straightforward Gait Speed [20,21], as well as the Modified Mini-Mental Score [22] or the Short Portable Mental Status Questionnaire [23].