Prognostic significance of the Medical Research Council cytogenetic classification compared with the European LeukaemiaNet risk classification system in acute myeloid leukaemia.
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SUBMITTER: Kadia T
PROVIDER: S-EPMC4977576 | biostudies-literature | 2015 Aug
REPOSITORIES: biostudies-literature
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Prognostic significance of the Medical Research Council cytogenetic classification compared with the European LeukaemiaNet risk classification system in acute myeloid leukaemia.
Kadia Tapan T Kantarjian Hagop H Garcia-Manero Guillermo G Borthakur Gautam G Wang Xuemei X Patel Keyur K Jabbour Elias E Brandt Mark M Daver Naval N Pemmaraju Naveen N Pierce Sherry S Cortes Jorge J Ravandi Farhad F
British journal of haematology 20150225 4
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Project description:Chromosome banding analysis is the gold standard method for the identification of recurrent cytogenetic abnormalities in acute myeloid leukaemia (AML). It allows stratification of AML patients into subgroups with distinct responses to therapy and survival. Unfortunately, a variety of issues hamper cytogenetic evaluation in c. 10% of cases [unsuccessful cytogenetics (UC)] and the outcome of these patients is poorly understood. To better define the significance of UC in patients with AML, we compared the baseline characteristics and the prognostic impact of 94 (6%) patients, whose standard metaphase analysis yielded unacceptable results, to the remaining 1403 AML patients with successful cytogenetic analysis treated on successive Southwestern Oncology Group protocols. The incidence of UC increased with age, with peak incidence in patients older than 60 years. These patients had a lower response rate to induction chemotherapy (complete remission rate of 43%) and dismal 5-year survival rates (16%), which was especially poor in patients older than 60 years (<5%). The complete remission and survival rates were similar to those seen in patients with unfavourable karyotype. The early death rate was not increased. These results suggest that UC increases with age and predict for poor outcomes, similar to the outcomes of patients with unfavourable karyotype.
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Project description:PurposeTo evaluate the prognostic significance of the international European LeukemiaNet (ELN) guidelines for reporting genetic alterations in acute myeloid leukemia (AML).Patients and methodsWe analyzed 1,550 adults with primary AML, treated on Cancer and Leukemia Group B first-line trials, who had pretreatment cytogenetics and, for cytogenetically normal patients, mutational status of NPM1, CEBPA, and FLT3 available. We compared complete remission (CR) rates, disease-free survival (DFS), and overall survival (OS) among patients classified into the four ELN genetic groups (favorable, intermediate-I, intermediate-II, adverse) separately for 818 younger (age < 60 years) and 732 older (age ≥ 60 years) patients.ResultsThe percentages of younger versus older patients in the favorable (41% v 20%; P < .001), intermediate-II (19% v 30%; P < .001), and adverse (22% v 31%; P < .001) genetic groups differed. The favorable group had the best and the adverse group the worst CR rates, DFS, and OS in both age groups. Both intermediate groups had significantly worse outcomes than the favorable but better than the adverse group. Intermediate-I and intermediate-II groups in older patients had similar outcomes, whereas the intermediate-II group in younger patients had better OS but not better CR rates or DFS than the intermediate-I group. The prognostic significance of ELN classification was confirmed by multivariable analyses. For each ELN group, older patients had worse outcomes than younger patients.ConclusionThe ELN classification clearly separates the genetic groups by outcome, supporting its use for risk stratification in clinical trials. Because they have different proportions of genetic alterations and outcomes, younger and older patients should be reported separately when using the ELN classification.
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