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It is likely that many different mutations and\/or epigenetic aberrations can produce the same disease, with these differences responsible for the very variable response to therapy, which is AML's principal clinical feature.<\/jats:p><jats:p><jats:italic>Diagnosis:<\/jats:italic> This rests on demonstration that the marrow or blood has &gt;20% blasts of myeloid lineage. Blast lineage is assessed by multiparameter flow cytometry with CD33 and CD13 being surface markers typically expressed by myeloid blasts. It should be realized that clinical\/prognostic considerations, not the blast % per se, should be the main factor determining how a patient is treated.<\/jats:p><jats:p><jats:italic>Risk stratification:<\/jats:italic> Two features determine risk: the probability of treatment\u2010related mortality (TRM) and, more important, even in patients aged &gt;75 with Zubrod performance status 1, the probability of resistance to standard therapy despite not incurring TRM. The chief predictor of resistance is cytogenetics with a monosomal karyotype (MK) denoting the disease is essentially incurable with standard therapy even if followed by a standard allogeneic transplant (HCT). The most common cytogenetic finding is a normal karyotype (NK) and those of such patients with an NPM1 mutation but no FLT3 internal tandem duplication (ITD), or with a CEBPA mutation, have a prognosis similar to that of patients with the most favorable cytogenetics [inv(16) or t(8;21)] (60\u201370% cure rate). In contrast, NK patients with a FLT3 ITD have only a 30\u201340% chance of cure even after HCT. Accordingly analyses of NPM1, FLT3, and CEBPA should be part of routine evaluation, much as is cytogenetics. Risk is best assessed considering several variables simultaneously rather than, for example, only age.<\/jats:p><jats:p><jats:italic>Risk\u2010adapted therapy:<\/jats:italic> Patients with inv(16) or t(8;21) or who are NPM1+\/FLT3ITD\u2212 can receive standard therapy (daunorubicin + cytarabine) and should not receive HCT in first CR. It seems likely that use of a daily daunorubicin dose of 90 mg\/m<jats:sup>2<\/jats:sup> will further improve outcome in these patients. There appears no reason to use doses of cytarabine &gt; 1 g\/m<jats:sup>2<\/jats:sup> (for example, bid \u00d7 6 days), as opposed to the more commonly used 3 g\/m<jats:sup>2<\/jats:sup>. Patients with an unfavorable karyotype (particularly MK) are unlikely to benefit from standard therapy (even with dose escalation) and are thus prime candidates for clinical trials of new drugs or new approaches to HCT; the latter should be done in first CR. Patients with intermediate prognoses (for example, NK and NPM and FLT3ITD negative) should also receive HCT in first CR and can plausibly receive either investigational or standard induction therapy, with the same prognostic information about standard therapy leading one patient to choose the standard and another an investigational option. Am. J. Hematol. 87:90\u201399, 2012. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.22246","type":"journal-article","created":{"date-parts":[[2011,12,17]],"date-time":"2011-12-17T06:39:18Z","timestamp":1324103958000},"page":"89-99","source":"Crossref","is-referenced-by-count":114,"title":["Acute myeloid leukemia: 2012 update on diagnosis, risk stratification, and management"],"prefix":"10.1002","volume":"87","author":[{"given":"Elihu H.","family":"Estey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,12,17]]},"reference":[{"key":"e_1_2_13_2_2","volume-title":"SEER Cancer Statistics Review 1975\u20132008; National Cancer Institute","author":"Howlader 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