We have evaluated 9 new molecular markers (ERG, EVI1, MLL-PTD, MN1, PRAME, RHAMM, and WT1 gene-expression levels plus FLT3 and NPM1 mutations) in 121 de novo cytogenetically normal acute myeloblastic leukemias. In the multivariate analysis, high ERG or EVI1 and low PRAME expressions were associated with a shorter relapse-free survival (RFS) and overall survival (OS). A 0 to 3 score was given by assigning a value of 0 to favorable parameters (low ERG, low EVI1, and high PRAME) and 1 to adverse parameters. This model distinguished 4 subsets of patients with different OS (2-year OS of 79%, 65%, 46%, and 27%; P ؍ .001) and RFS (2-year RFS of 92%, 65%, 49%, and 43%; P ؍ .005
There is barely any information about the prognostic significance of FLT3 expression and mutational status in cytogenetically distinct subgroups of acute lymphoblastic leukemia (ALL). We analyzed the presence of FLT3-tyrosine kinase domain (TKD) and FLT3-internal tandem duplication (ITD) mutations as well as FLT3 expression levels in 54 newly diagnosed patients with B-ALL (n ¼ 49) or T-ALL (n ¼ 5). All B/T-ALL samples tested negative for the presence of FLT3-TKD or FLT3-ITD. None of the T-ALL and E2A-PBX1 þ B-ALL overexpressed FLT3. In contrast, mainly MLL-AF4 þ B-ALL but also ETV6-RUNX1 þ , BCR-ABL þ or B-ALL displaying normal cytogenetics exhibited significantly higher FLT3 expression levels than normal bone marrow, supporting that aberrantly increased transcription of FLT3, rather than activating FLT3 mutations, contributes to the pathogenesis of these B-ALL. Using the median FLT3 expression as cut-off value we found that high-level FLT3 expression is associated with an extremely poor 1-year overall survival (OS; 0 vs 71%; P ¼ 0.002) and disease-free survival (DFS; 0 vs 43%; P ¼ 0.03) in MLL-AF4 þ B-ALL but not in MLL-germline B-ALL. Cox regression analysis with OS/DFS as end points showed that age414 years and high-level FLT3 expression were independent prognostic factors when all ALL patients were analyzed together. Importantly, when the MLL-AF4 þ B-ALL subgroup was analyzed separately, high-level FLT3 expression was the only independent prognostic factor for OS and treatment outcome. These findings indicate that high FLT3 expression identifies MLL-AF4 þ ALL patients at very high risk of treatment failure and poor survival, emphasizing the value of ongoing/future clinical trials for FLT3 inhibitors.
Although transfusion is certainly a common practice in PCPs, there is a relative lack of literature on this topic. Publications are unconnected and hardly any prospective studies have been performed. A large part of the little literature available only concerns descriptive and very general aspects of the issue. As transfusional products and financial and human resources are finite, it would be desirable to establish clear research lines on the different aspects considered (clinical, infrastructure, and ethical) that can help clinicians, nurses, patients, and carers to make a decision.
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