Arsenic trioxide in front-line therapy of acute promyelocytic leukemia (C9710): prognostic significance of FLT3 mutations and complex karyotype. Issue 7 (July 2014)

• Record Type: Journal Article
• Authors: Poiré, Xavier; Moser, Barry K.; Gallagher, Robert E.; Laumann, Kristina; Bloomfield, Clara D.; Powell, Bayard L.; Koval, Gregory; Gulati, Kabir; Holowka, Nicholas; Larson, Richard A.; Tallman, Martin S.; Appelbaum, Frederick R.; Sher, Dorie; Willman, Cheryl; Paietta, Elisabeth; Stock, Wendy
• Is Part Of: Leukemia & lymphoma. Volume 55:Issue 7(2014:Jul.)
• Page Start: 1523
• Page End: 1532
• Publication Date: 2014-07
• Subjects: Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2013.842985
• Languages: English
• ISSNs: 1042-8194

Abstract

<abstract> <title>Abstract</title> <p>The addition of arsenic trioxide (ATO) to frontline therapy of acute promyelocytic leukemia (APL) has been shown to result in significant improvements in disease-free survival (DFS). <italic>FLT3</italic> mutations are frequently observed in APL, but its prognostic significance remains unclear. We analyzed 245 newly diagnosed adult patients with APL treated on intergroup trial C9710 and evaluated previously defined biological and prognostic factors and their relationship to <italic>FLT3</italic> mutations and to additional karyotypic abnormalities. <italic>FLT3</italic> mutations were found in 48% of patients, including 31% with an internal tandem duplication (<italic>FLT3</italic>-ITD), 14% with a point mutation (<italic>FLT3</italic>-D835) and 2% with both mutations. The <italic>FLT3</italic>-ITD mutant level was uniformly low, < 0.5. Neither <italic>FLT3</italic> mutation had an impact on remission rate, induction death rate, DFS or overall survival (OS). The addition of ATO consolidation improved outcomes regardless of <italic>FLT3</italic> mutation type or level, initial white blood cell count, <italic>PML–RARA</italic> isoform type or transcript level. The presence of a complex karyotype was strongly associated with an inferior OS independently of post-remission treatment. In conclusion, the addition of ATO to frontline therapy overcomes the impact of previously described adverse prognostic factors including <italic>FLT3</italic> mutations. However, complex karyotype is strongly associated with an inferior OS despite ATO therapy.</p> </abstract>