AML refractory to primary induction with Ida-FLAG has a poor clinical outcome. (May 2018)

• Record Type: Journal Article
• Authors: Kavanagh, Simon; Heath, Emily; Hurren, Rose; Gronda, Marcela; Barghout, Samir H.; Liyanage, Sanduni U.; Siriwardena, Thirushi P.; Claudio, Jaime; Zhang, Tong; Sukhai, Mahadeo; Stockley, Tracy L.; Kamel-Reid, Suzanne; Rostom, Amr; Lutynski, Andrzej; Khalaf, Dina; Rydlewski, Anna; Chan, Steven M.; Gupta, Vikas; Maze, Dawn; Sibai, Hassan; Schuh, Andre C.; Yee, Karen; Minden, Mark D.; Schimmer, Aaron D.
• Is Part Of: Leukemia research. Volume 68(2018)
• Page Start: 22
• Page End: 28
• Publication Date: 2018-05
• Subjects: AML -- Chemotherapy -- Molecular genetics -- Chemosensitivity; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2018.02.012
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: Those refractory to Ida-FLAG induction have a dismal prognosis. High risk cytogenetics and TP53 mutations are associated with refractoriness. The dominant genetic mutation persists in patients refractory to Ida-FLAG induction. Abstract: We evaluated outcomes of 100 patients with high risk AML treated with Ida-FLAG induction as first-line therapy. 72 achieved remission with one cycle; 19 did not. High risk cytogenetics and TP53 mutations were associated with failure to achieve remission. In those reaching remission, allogeneic bone marrow transplantation was associated with better relapse-free and overall survival. Those not achieving remission with induction therapy were extremely unlikely to reach remission with further therapy and had a dismal prognosis. Exploratory molecular analysis confirmed persistence of the dominant genetic mutations identified at diagnosis. Ex vivo chemosensitivity did not demonstrate significant differences between responders and non-responders. Thus, Ida-FLAG induction has a high chance of inducing remission in patients with high risk AML. Those achieving remission require allogeneic transplantation to achieve cure; those not achieving remission rarely respond to salvage chemotherapy and have a dismal outcome. Alternatives to conventional chemotherapy must be considered in this group.