Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm Export

@article{citeulike:5950099, abstract = {To assess the prognostic relevance of activating mutations of the FLT3 gene in homogeneously treated adults 16 to 60 years of age with acute myeloid leukemia (AML) and normal cytogenetics, pretreatment samples from 224 patients entered into 2 consecutive multicenter treatment trials were analyzed for FLT3 internal tandem duplications (ITDs) and Asp835 mutations. Treatment included intensive double-induction therapy and postremission therapy with high cumulative doses of high-dose cytarabine. ITDs were detected in 32\% of the patients and were related to de novo AML and to high white blood cell (WBC) counts, percentages of peripheral blood (PB) and bone marrow (BM) blasts, and serum lactate dehydrogenase levels. Asp835 mutations were present in 14\% of the patients and were associated with WBC counts and percentages of PB and BM blasts that were higher than those of patients without FLT3 mutations. With a median follow-up of 34 months, remission duration and overall survival (OS) were significantly shorter for patients with Asp835 mutations or an ITD than for those without FLT3 mutations (P = .03 and P = .0004, respectively). These results were attributable mainly to the negative prognostic effect of FLT3 ITDs. On multivariate analysis, mutant FLT3 was an independent marker affecting remission duration and OS (hazard ratio, 2.35 and 2.11, respectively). Fluorescence in situ hybridization did not detect monoallelic FLT3 deletions in ITD-positive patients. FLT3 mutations identify a subset of young AML patients with normal cytogenetics who do not benefit from intensive chemotherapy, including double-induction and postremission therapy with high-dose cytarabine. 10.1182/blood-2002-05-1440}, author = {Frohling, Stefan and Schlenk, Richard F. and Breitruck, Jochen and Benner, Axel and Kreitmeier, Sylvia and Tobis, Karen and Dohner, Hartmut and Dohner, Konstanze}, citeulike-article-id = {5950099}, citeulike-linkout-0 = {http://dx.doi.org/10.1182/blood-2002-05-1440}, citeulike-linkout-1 = {http://bloodjournal.hematologylibrary.org/content/100/13/4372.abstract}, citeulike-linkout-2 = {http://bloodjournal.hematologylibrary.org/content/100/13/4372.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/12393388}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=12393388}, day = {15}, doi = {10.1182/blood-2002-05-1440}, journal = {Blood}, keywords = {aml, flt3}, month = {December}, number = {13}, pages = {4372--4380}, posted-at = {2009-10-16 10:18:53}, priority = {2}, title = {Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm}, url = {http://dx.doi.org/10.1182/blood-2002-05-1440}, volume = {100}, year = {2002} }

TY - JOUR ID - citeulike:5950099 L3 - citeulike-article-id:5950099 N2 - To assess the prognostic relevance of activating mutations of the FLT3 gene in homogeneously treated adults 16 to 60 years of age with acute myeloid leukemia (AML) and normal cytogenetics, pretreatment samples from 224 patients entered into 2 consecutive multicenter treatment trials were analyzed for FLT3 internal tandem duplications (ITDs) and Asp835 mutations. Treatment included intensive double-induction therapy and postremission therapy with high cumulative doses of high-dose cytarabine. ITDs were detected in 32% of the patients and were related to de novo AML and to high white blood cell (WBC) counts, percentages of peripheral blood (PB) and bone marrow (BM) blasts, and serum lactate dehydrogenase levels. Asp835 mutations were present in 14% of the patients and were associated with WBC counts and percentages of PB and BM blasts that were higher than those of patients without FLT3 mutations. With a median follow-up of 34 months, remission duration and overall survival (OS) were significantly shorter for patients with Asp835 mutations or an ITD than for those without FLT3 mutations (P = .03 and P = .0004, respectively). These results were attributable mainly to the negative prognostic effect of FLT3 ITDs. On multivariate analysis, mutant FLT3 was an independent marker affecting remission duration and OS (hazard ratio, 2.35 and 2.11, respectively). Fluorescence in situ hybridization did not detect monoallelic FLT3 deletions in ITD-positive patients. FLT3 mutations identify a subset of young AML patients with normal cytogenetics who do not benefit from intensive chemotherapy, including double-induction and postremission therapy with high-dose cytarabine. 10.1182/blood-2002-05-1440 IS - 13 JF - Blood EP - 4380 TI - Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm VL - 100 SP - 4372 KW - aml KW - flt3 AU - Frohling, Stefan AU - Schlenk, Richard AU - Breitruck, Jochen AU - Benner, Axel AU - Kreitmeier, Sylvia AU - Tobis, Karen AU - Dohner, Hartmut AU - Dohner, Konstanze PY - 2002/12/15/ UR - http://dx.doi.org/10.1182/blood-2002-05-1440 ER -