Editorial Volume 3 Issue 3 - October 2018 DOI: 10.19080/JTMP.2018.03.555615 J Tumor Med Prev Copyright © All rights are reserved by Nahla AM Hamed Acute Myeloid Leukemia in Patients Older than 60 Year Nahla AM Hamed* Department of Hematology, Alexandria University, Egypt Submission: September 04, 2018; Published: October 09, 2018 *Corresponding author: Nahla AM Hamed, Faculty of Medicine, Department of Hematology, Alexandria University, Egypt, Email: Introduction The median age of AML at diagnosis is 67 years with 54% of patients diagnosed at 65 years or older (and approximately a third diagnosed at >75 years of age) [1]. Older AML, defined as patients aged >60 years, has been one of the most challenging subsets to stratify and derive treatment decisions [2]. Determinants of treatment failure in older AML The determinants of treatment success and failure remain partly understood. A combination of patient-related and specific disease-related factors are more common among this aging population and correlate markedly with treatment failure (i.e., primary resistance and relapse after induction therapy). They include comorbid conditions, performance status, decreased drug clearance and prolonged exposure to chemotherapeutics resulting from pharmacokinetic and pharmacodynamic changes, less tolerability to infections due to decreased immune competence of elderly patients, psychosocial factors (cognitive decline, social isolation, and, often, lack of caretakers), multidrug resistant abilities of the leukemia cells to expel the chemotherapeutics, antecedent hematologic disorders [3] (previous MDS, chronic myelomonocytic leukemia, myeloproliferative neoplasm), prior exposure to cytotoxic therapy for other disorders [4] and higher frequencies of adverse cytogenetics and unfavorable molecular aberrations [3]. Cytogenetic and molecular changes The percentage of favorable cytogenetics (t(8;21), in- v(16)/t(16;16), and t(15;17)) decreased to a low percentage among the oldest age groups (<5% for patients older than 70 years;). No significant difference in frequency between patients who were not in the favorable or adverse cytogenetic group in different age groups. The rate of unfavorable risk cytogenetics increased continuously up to 36% in patients older than 85 years [5]. Chromosome 5 and 7 aberrations increase in the oldest age groups while complex karyotypes increase continuously up to 28% in the oldest age group. Trisomy 8 as a sole aberration was found more frequent in older patients than other age groups [5]. Monosomal karyotype increased with age to 20% in patients older than 60 years [1]. The median age of patients with chromosomal aneuploidy and TP53 mutations is 58 years as opposed to 49 years for the patients with aneuploidy alone. Chromosomal aneuploidy, and TP53 mutations are enriched in older AML (49% of >60 year-olds belong to either group) [2]. The high frequency of complex karyotypes and unbalanced aberrations in older patients indicates multiple genetic events, including epigenetic changes during a lifetime, a prolonged duration of exposure to environmental carcinogens which correlates with the number of mutations (especially in patients older than 60 years), and an accumulation of mutations from genetic error events in cell division. It has been demonstrated that clonal hematopoietic cells from normal individuals also accumulate mutations as a function of age [5]. RUNX1, ASXL1 and TP53 mutations (ELN adverse-risk category) are common in very old patient [6]. The frequency J Tumor Med Prev 3(3): JTMP.MS.ID.555615 (2018) 0053 Abstract Intensive remission induction chemotherapy should be considered by clinicians as the first choice for selected very old AML patients whenever feasible on clinical grounds. Early death in most studies does not seem to play a major role in the inferior outcome of elderly AML patients. The early death rate in intensively-treated patients has decreased considerably over the last 2 decades, most probably owing to better supportive care. Abbreviations: AML: Acute Myeloid Leukemia; OS: Overall Survival; CR: Complete Remission; HMAs: Hypomethylating Agents; DAC: Decitabine; AZA: Azacitidine; LDAC: Low-Dose Cytarabine; BSC: Best Supportive Care; ICT: Intensive Chemotherapy; RIC: Reduced Intensity Conditioning