PubMed · 10319696
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T Lebret, H Botto. 1999-02-15. [Acute prostatitis].. https://pubmed.ncbi.nlm.nih.gov/10319696/
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Between May 1988 and June 2000, 698 children were treated in the Medical Research Council acute myeloid leukemia 10 and 12 trials. The presenting features and outcomes of therapy in these children were compared by age. Although there was no single cutoff in age, younger children were more likely to have intermediate risk and less likely to have favorable cytogenetics (P <.001), and they had a higher incidence of translocations involving chromosome 11q23 (P <.001). The distribution of French-American-British (FAB) types also varied with age; FAB types M5 (P <.001) and M7 (P <.001) were more common in early childhood, whereas older children were more likely to have FAB types M0 (P =.03), M1 (P =.04), M2 (P =.005), and M3 (P <.001). Involvement of the central nervous system at diagnosis was also more common in the youngest children (P =.01). Younger children had more severe diarrhea (P =.002), whereas older children had worse nausea and vomiting (P =.01) after chemotherapy. When adjusted for other important factors, complete remission rates were similar (P =.5) and although there was less resistant disease in younger children (P =.003), this was partially balanced by a slight increase in deaths during induction therapy in younger patients (P =.06). On multivariate analysis overall survival (P =.02), event-free survival (P =.02), and disease-free survival were better (P =.06) in younger children due to a lower relapse rate (P =.02) especially in the bone marrow (P =.02).
Early response to therapy is one of the most important prognostic factors in acute leukemia. It is hypothesized that early immunophenotypical evaluation may help identify patients at high risk for relapse from those who may remain in complete remission (CR). Using multiparametric flow cytometry, the level of minimal residual disease (MRD) was evaluated in the first bone marrow (BM) in morphologic CR obtained after induction treatment from 126 patients with acute myeloid leukemia (AML) who displayed aberrant phenotypes at diagnosis. Based on MRD level, 4 different risk categories were identified: 8 patients were at very low risk (fewer than 10(-4) cells), and none have relapsed thus far; 37 were at low risk (10(-4) to 10(-3) cells); and 64 were at intermediate risk (fewer than 10(-3) to 10(-2) cells), with 3-year cumulative relapse rates of 14% and 50%, respectively. The remaining 17 patients were in the high-risk group (more than 10(-2) residual aberrant cells) and had a 3-year relapse rate of 84% (P =.0001). MRD level not only influences relapse-free survival but also overall survival (P =.003). The adverse prognostic impact was also observed when M3 and non-M3 patients with AML were separately analyzed, and was associated with adverse cytogenetic subtypes, 2 or more cycles to achieve CR, and high white blood cell counts. Multivariate analysis showed that MRD level was the most powerful independent prognostic factor, followed by cytogenetics and number of cycles to achieve CR. In conclusion, immunophenotypical investigation of MRD in the first BM in mCR obtained after AML induction therapy provides important information for risk assessment in patients with AML.
In acute myeloid leukemia (AML), further prognostic determinants are required in addition to cytogenetics to predict patients at increased risk of relapse. Recent studies have indicated that an internal tandem duplication (ITD) in the FLT3 gene may adversely affect clinical outcome. This study evaluated the impact of a FLT3/ITD mutation on outcome in 854 patients, mostly 60 years of age or younger, treated in the United Kingdom Medical Research Council (MRC) AML trials. An FLT3/ITD mutation was present in 27% of the patients and was associated with leukocytosis and a high percentage of bone marrow blast cells (P <.001 for both). It had a borderline association with a lower complete remission rate (P =.05) and a higher induction death rate (P =.04), and was associated with increased relapse risk (RR), adverse disease-free survival (DFS), event-free survival (EFS), and overall survival (OS) (P <.001 for all). In multivariate analysis, presence of a mutation was the most significant prognostic factor predicting RR and DFS (P <.0001) and was still significant for OS (P =.009) and EFS (P =.002). There was no evidence that the relative effect of a FLT3/ITD differed between the cytogenetic risk groups. More than one mutation was detected in 23% of FLT3/ITD(+) patients and was associated with worse OS (P =.04) and EFS (P =.07). Biallelic disease or partial/complete loss of wild-type alleles was present in 10% of FLT3/ITD(+) patients. The suggestion is made that detection of a FLT3/ITD should be included as a routine test at diagnosis and evaluated for therapeutic management.