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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 =

BACKGROUND Chronic myeloid leukemia (CML) may progress to blast phase (BP) at the rate of 1% to 1.5% per year. With the use of single-agent tyrosine kinase inhibitors, median overall survival ranges between 7 and 11 months. METHODS The outcome was analyzed for 42 patients with lymphoid BP-CML who were treated with hyperfractionated cyclophosphamide, vincristine, Adriamycin, dexamethasone (HCVAD) plus imatinib or dasatinib. RESULTS Complete hematological response was achieved in 90% of patients, complete cytogenetic remission in 58%, and complete molecular remission in 25%. Flow cytometry minimal residual disease negativity was achieved by 42% of evaluable patients after induction. Eighteen patients received allogeneic stem cell transplant (SCT) while in first complete hematological response. Median remission duration was 14 months and was longer among SCT recipients (P = .01) on multivariate analysis. Median overall survival was 17 months (range, 7-27 months) and was longer among SCT recipients (P

FMS-like tyrosine kinase III (FLT3) mutations occur in one-third of acute myeloid leukemia (AML) patients and predict poor outcome. The incidence and impact of FLT3 in myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) is unknown. We conducted a retrospective review to identify WHO MDS and CMML patients with FLT3 mutations at diagnosis. A total of 2,119 patients with MDS and 466 patients with CMML were evaluated at MD Anderson between 1997 and 2010. Of these, FLT3 mutation analysis was performed on 1,232 (58%) MDS and 302 (65%) CMML patients. FLT3 mutations were identified in 12 (0.95%) MDS patients: 9 (75%) had FLT3-ITD mutation and 3 had FLT3-tyrosine kinase domain (TKD) mutation. MDS patients with FLT3 mutations were younger (P = 0.02) and presented as RAEB (P = 0.03) more frequently. Median overall survival (OS) for FLT3-mutated MDS patients was 19.0 months versus 16.4 months for FLT3-nonmutated MDS patients (P = 0.08). FLT3 mutations were identified in 13 (4.3%) CMML patients: 8 had FLT3-ITD mutation and 5 had FLT3-TKD mutation. There were no significant differences in demographic and disease characteristics among CMML patients with and without FLT3 mutations. Median OS for FLT3-mutated CMML patients was 10.8 months versus 21.3 months for FLT3-nonmutated CMML patients (P = 0.12). FLT3 occurs in MDS and CMML at a lower frequency than AML and does not predict poor outcome.

BACKGROUND: The impact of single versus multiple fms-like tyrosine kinase receptor 3 internal tandem duplication (FLT3-ITD) mutations on the clinical outcome of patients with acute myelogenous leukemia has not been well studied, and particularly has not been investigated while simultaneously accounting for the quantitative mutation burden. METHODS: The authors conducted a multivariate analysis of overall survival, event-free survival, and complete remission duration, including numeric variation (single vs multiple) and quantitative mutant burden of FLT3-ITD as variables among other clinically relevant factors. RESULTS: An analysis of a cohort of 1043 patients with AML demonstrated that, among patients with normal-karyotype acute myelogenous leukemia and FLT3-ITD mutation, overall survival and event-free survival were not affected by the number of FLT3-ITD mutations, but complete remission duration was significantly longer in patients who had multiple FLT3-ITD mutations (median, 86 weeks vs 34 weeks; P = .03). CONCLUSIONS: The current results indicated that time-to-event analyses of patients with normal-karyotype acute myelogenous leukemia and FLT3-ITD mutation should take into account the number of mutations and the mutant burden, among other factors. Cancer 2012. © 2012 American Cancer Society.

BACKGROUND: Activating mutations in RAS are frequently present in patients with acute myeloid leukemia (AML), but their overall prognostic impact is not clear. METHODS: A retrospective analysis was performed to establish the clinical characteristics of patients with RAS-mutated (RASmut) AML, to analyze their outcome by therapy, and to describe the proteomic profile of RASmut compared with wild-type RAS (RASWT) AML. RESULTS: Of 609 patients with newly diagnosed AML, 11% had RASmut. Compared with RASWT, patients with RASmut AML were younger (median age, 54 years vs 63 years; P = .001), had a higher white blood cell count (16K mm−3 vs 4K mm−3 ; P < 0.001) and bone marrow blast percentage (56% vs 42%; P = .01) at diagnosis, and were less likely to have an antecedent hematologic disorder (36% vs 50%; P = .03). The inv(16) karyotype was overrepresented in patients with RASmut and the −5 and/or −7 karyotype was underrepresented. RAS mutations were found to have no prognostic impact on overall survival or disease-free survival overall or within cytogenetic subgroups. There was a suggestion that patients with RASmut benefited from cytarabine (AraC)-based therapy. Proteomic analysis revealed simultaneous upregulation of the RAS-Raf-MAP kinase and phosphoinositide 3-kinase (PI3K) signaling pathways in patients with RASmut. CONCLUSIONS: RAS mutations in AML may delineate a subset of patients who benefit from AraC-based therapy and who may be amenable to treatment with inhibitors of RAS and PI3K signaling pathways. Cancer 2012. © 2012 American Cancer Society.