title: Improvement in clinical outcome of FLT3 ITD mutated acute myeloid leukemia patients over the last one and a half decade.
abstract: AML with FLT3 ITD mutations are associated with poor outcome. We reviewed outcomes of patients with FLT3 ITD mutated AML to investigate trends over time. We analyzed 224 AML patients (excluding patients with core binding factor and acute promyelocytic leukemia) referred to our institution between 2000 and 2014. Patients were divided into five cohorts by era: 2000-2002 (Era 1, n = 19), 2003-2005 (Era 2, n = 41), 2006-2008 (Era 3, n = 53), 2009-2011 (Era 4, n = 55), and 2012-2014 (Era 5, n = 56) to analyze differences in outcome. The baseline characteristics were not statistically different across Eras. The response rate (CR/CRp) from Era 1-5 was 68%, 49%, 72%, 73%, and 75%, respectively. The overall response rate (all Eras) with chemotherapy alone versus chemotherapy plus FLT3 inhibitor was 67% and 72.5%, respectively (P = 0.4). The median time to relapse was 6, 3.6, 7.9, 8.1 months and not reached from Eras 1 through 5, respectively (P = 0.001). The median OS has improved: 9.6, 7.6, 14.4, 15.7, and 17.8 month from Eras 1-5, respectively (P = <0.001). Stem cell transplant as a time-dependent variable, showed better OS in the univariate analysis (HR: 0.57, 95% CI: 0.39-0.84, P = 0.004) but did not retained its significance in multivariate analysis (HR: 0.75, 95% CI: 0.50-1.13, P = 0.16). Our data suggest improvement in outcome of FLT3 ITD mutated AML patients over the last 15 years. This is probably due to improvement in treatment strategies, including but not limited to integration of FLT3 inhibitors and increased use of SCT.
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Talha
authors: T
authors: Badar
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Hagop M
authors: HM
authors: Kantarjian
authors: Graciela M
authors: GM
authors: Nogueras-Gonzalez
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Gautam
authors: G
authors: Borthakur
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Guillermo
authors: G
authors: Garcia Manero
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Michael
authors: M
authors: Andreeff
authors: Department of Leukemia, Section of Molecular Hematology and Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Marina
authors: M
authors: Konopleva
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Tapan M
authors: TM
authors: Kadia
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Naval
authors: N
authors: Daver
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: William G
authors: WG
authors: Wierda
authors: Department of Leukemia, Section of Molecular Hematology and Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Raja
authors: R
authors: Luthra
authors: Department of Leukemia, Section of Molecular Hematology and Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Keyur
authors: K
authors: Patel
authors: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Betul
authors: B
authors: Oran
authors: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Richard
authors: R
authors: Champlin
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Farhad
authors: F
authors: Ravandi
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Jorge E
authors: JE
authors: Cortes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D000077157:Sorafenib; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3