Abstract:
:Despite progress in AML therapy, most patients eventually relapse, even the ones with normal or favorable karyotype. Since survival is poor once relapse occurs, new genetic tools above karyotype at diagnosis are needed to predict leukemia free survival. Recently, Flt3/ITD has been reported as an independent marker for clinical outcome in most studies concerning adult AML patients. To assess the prognostic relevance of activating mutations of Flt3, pretreatment samples of 100 not-M3 AML patients, all of them subjected to an intensive chemotherapy regimen, were analyzed for Flt3/ITD; 25/100 patients had one or more Flt3-ITD. Flt3/ITD patients had higher WBC count (P = 0.005), a lower incidence of a preceding MDS (P = 0.004) and most of them had a normal karyotype. Flt3/ITD had no impact on CR achievement while karyotype remained the most powerful prognostic factor (HR 2.8 95% CI 1.2 6.3). However, post-remission outcome was significantly worsened by the presence of Flt3/ITD. Median RFS of the Flt3/ITD patients was 5 vs. 27 months compared to the patients with wild-type Flt3 (P = 0.0002); moreover, Flt3/ITD patients had a significantly poorer post-remission survival (11 vs. 38 months, P = 0.01). On multivariate analysis, the presence of Flt3-ITD significantly affected relapse free survival and post-remission survival (HR 3.1 and 2.1, respectively). Thus, post-remission outcome highly depends on Flt3 status. Flt3 mutations identify patients at high risk of relapse, who should prospectively receive, according to age, either more aggressive or alternative therapeutic approaches.
journal_name
Leuk Lymphomajournal_title
Leukemia & lymphomaauthors
Ciolli S,Vannucchi AM,Leoni F,Nozzoli C,Longo G,Salati A,Pancrazzi A,Bianchi L,Gigli F,Bosi Adoi
10.1080/1042819031000151851keywords:
subject
Has Abstractpub_date
2004-01-01 00:00:00pages
73-8issue
1eissn
1042-8194issn
1029-2403journal_volume
45pub_type
杂志文章abstract::There is increasing evidence for an interaction between acute leukemia cells and the microenvironment of the bone marrow. Blast cells from cases of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) bind to cellular and extracellular matrix components of the bone marrow stroma. In AML, adhesion to str...
journal_title:Leukemia & lymphoma
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