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|Ref Type||Journal Article|
|Authors||Büchner T, Berdel WE, Haferlach C, Haferlach T, Schnittger S, Müller-Tidow C, Braess J, Spiekermann K, Kienast J, Staib P, Grüneisen A, Kern W, Reichle A, Maschmeyer G, Aul C, Lengfelder E, Sauerland MC, Heinecke A, Wörmann B, Hiddemann W|
|Title||Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: a study by the German Acute Myeloid Leukemia Cooperative Group.|
|Journal||Journal of clinical oncology : official journal of the American Society of Clinical Oncology|
|Date||2009 Jan 01|
|Abstract Text||The purpose of the study was to assess the contribution of age and disease variables to the outcome of untreated patients with acute myeloid leukemia (AML) receiving varying intensive induction chemotherapy.Patients 16 to 85 years of age with primary AML, known karyotype, and uniform postremission chemotherapy enrolled onto two consecutive trials were eligible and were randomly assigned to induction either with a standard-dose (cytarabine, daunorubicin, and 6-thioguanine) and a high-dose (cytarabine and mitoxantrone) combination, or with two courses of the high-dose combination. Subgroups were defined by karyotype, nucleophosmin and FLT3 mutation, WBC count, serum lactate dehydrogenase, and residual blasts.In 1,284 patients, the overall survival at 4 years in those younger and older than 60 years was 37% versus 16% (P < .001) and the ongoing remission duration was 46% versus 22% (P < .001). Similar age-related differences in outcome were found for all defined subgroups. No difference in outcome according to randomly assigned treatment regimen was observed in any age group or prognostic subset. Regarding prognostic subgroups, molecular factors were also considered.Under harmonized conditions, older and younger patients with AML show modest differences in their risk profiles and equally no dose response to intensified chemotherapy. Their observed fundamental difference in outcome across all subgroups remains unexplained. Further molecular investigation may elucidate the age effect in AML and identify new targets.|
|Molecular Profile||Treatment Approach|
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|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|NPM1 mutant||acute myeloid leukemia||not applicable||N/A||Clinical Study||Prognostic||In multiple clinical studies, an NPM1 mutation without FLT3 internal tandem duplication (ITD) mutation was associated with favorable prognosis in acute myeloid leukemia (AML) patients, compared to AML patients harboring an NPM1 mutation and FLT3 ITD mutation (PMID: 19047294, PMID: 24573385, PMID: 25713434).||25713434 19047294 24573385|