2012, Number 4
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ABSTRACTAcute myeloblastic leukemia (AML) has a high morbility and mortality related to high early relapse rates and frequent refractory disease. Among the prognostic factors used for stratifying the disease risk are the age, the white blood cell count at diagnosis, the cytogenetics, the AML etiology ( chemotherapy related or neoplasia related); despite these factors there is no accurate marker to define risk of refractory or uncontrolled disease. The FLT3 receptor mutations, specifically internal tandem duplication mutations (ITD-FLT3), have been associated with adverse outcome and high relapse rates despite the intensive treatment schemes including chemotherapy plus specific FLT3 inhibitors or allogeneic stem cell transplantation. Attemps to correlate FLT3 mutations with cytogenetics have found several associations between normal cytogenetics or intermediate risk and the ITD-FLT3 mutations, some favor the prognostic and others do not. Currently there are investigations trying to define the role of the FLT3 inhibitors and other drugs directed to overcome the different pathophysiological mechanisms involved in AML. This article is intended to review the state of knowledge of FLT3 mutations and its impact on the clinical course of AML.
Ruiz-Arguelles GJ, Garcés-Eisele J, Alarcón-Urdaneta C, Lutz-Presno J, Ruiz-Delgado GJ. Primary FMS-like tyrosine kinase 3 (FLT3) mutations in Mexican mestizo patients with de novo acute myelogenous leukemia. Presentado como cartel en XXXIV World Congress - ISH / LIII Congreso Nacional - AMEH, Cancún , Abril de 2012.
Stone RM, Fischer T, Paquette R, et al. A Phase 1b study of midostaurin (PKC412) in combination with daunorubicin and cytarabine induction and high-dose cytarabine consolidation in patients under age 61 with newly diagnosed de novo acute myeloid leukemia: overall survival of patients whose blasts have FLT3 mutations is similar to those with wild-type FLT3. Blood 2009;114:263.
Stone RM, Dohner H, Ehninger G, Villeneuve M, Teasdale T, Virkus JD, et al. CALGB 10603 (RATIFY): a randomized phase III study of induction (daunorubicin/cytarabine) and consolidation (high-dose cytarabine) chemotherapy combined with midostaurin or placebo in treatment-naive patients with FLT3 mutated AML. J Clin Oncol 2011;29:31s.