{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:33:13Z","timestamp":1791070393513,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,25]],"date-time":"2013-03-25T00:00:00Z","timestamp":1364169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec><jats:title>Disease overview<\/jats:title><jats:p>Acute myeloid leukemia (AML) results from accumulation of abnormal blasts in the marrow. These cells interfere with normal hematopoiesis, can escape into the peripheral blood, and infiltrate CSF and lung. It is likely that many different mutations, epigenetic aberrations, or abnormalities in micro RNA expression can produce the same morphologic disease with these differences responsible for the very variable response to therapy, which is AMLs principal feature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Diagnosis<\/jats:title><jats:p>This rests on demonstration that the marrow or blood has\u2009&gt;\u200920% 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:sec><jats:sec><jats:title>Risk Stratification<\/jats:title><jats:p>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 cytogentic 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. Increasing evidence indicates that other mutations and abnormalities in microRNA (miRNA) expression also affect resistance as do post treatment factors, in particular the presence of minimal residual disease. These newer mutations and MRD are discussed in this update.<\/jats:p><\/jats:sec><jats:sec><jats:title>Risk\u2010adapted therapy<\/jats:title><jats:p>Patients with inv (16) or t(8;21) or who are NPM1+\/FLT3ITD\u2014can receive standard therapy (daunorubicin\u2009+\u2009cytarabine) 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\u2009&gt;\u20091 g\/m<jats:sup>2<\/jats:sup> (for example bid X 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. This update discusses results with newer agents: quizartinib and crenolanib, gemtuzumab ozogamicin, clofarabine and cladribine, azacitidine and decitabine, volasertib, and means to prevent relapse after allogeneic transplant.<\/jats:p><jats:p>The diagnosis of AML essentially is made as it was in 2012. Thus this review will emphasize new developments in risk stratification and treatment using as references many papers published in 2012. Am. J. Hematol. 88:318\u2013327, 2013. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajh.23404","type":"journal-article","created":{"date-parts":[[2013,3,25]],"date-time":"2013-03-25T08:19:42Z","timestamp":1364199582000},"page":"317-327","source":"Crossref","is-referenced-by-count":203,"title":["Acute myeloid leukemia: 2013 update on risk\u2010stratification and management"],"prefix":"10.1002","volume":"88","author":[{"given":"Elihu H.","family":"Estey","sequence":"first","affiliation":[{"name":"Division of Hematology University of Washington"},{"name":"Clinical Research Division Fred Hutchinson Cancer Research Center, Seattle, 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