Outcome of FLT3-ITD-positive acute myeloid leukemia: impact of allogeneic stem cell transplantation and tyrosine kinase inhibitor treatment

Fleischmann, Maximilian; Schnetzke, Ulf; Schrenk, Karin; Schmidt, Volker; Sayer, Herbert G.; Hilgendorf, Inken; Hochhaus, Andreas; Scholl, Sebastian

doi:10.1007/s00432-016-2290-5

Cited by 19 publications

(18 citation statements)

References 43 publications

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“…FLT3/ITD occurs in 20–30% of young adults with AML and is associated with poor prognosis. [293031] In the meta-analysis, we detect an association between FLT3-ITD positive and ERG expression ( OR = 3.8634, 95% CI :1.8285–8.1626, P = 0.004), in line with the previous report by Marcucci et al . [919]…”

Section: Discussionsupporting

confidence: 90%

E-26 Transformation-specific Related Gene Expression and Outcomes in Cytogenetically Normal Acute Myeloid Leukemia

Fang

Yuan

Song

et al. 2017

Chinese Medical Journal

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Background:The E-26 transformation-specific related gene (ERG) is frequently expressed in cytogenetically normal acute myeloid leukemia (CN-AML). Herein, we performed a meta-analysis to investigate the relationship between the prognostic significance of ERG expression and CN-AML.Methods:A systematic review of PubMed database and other search engines were used to identify the studies between January 2005 and November 2016. A total of 667 CN-AML patients were collected from seven published studies. Of the 667 patients underwent intensive chemotherapy, 429 had low expression of ERG and 238 had high expression of ERG. Summary odds ratio (OR) and the 95% confidence interval (CI) for the ERG expression and CN-AML were calculated using fixed- or random-effects models. Heterogeneity was assessed using Chi-squared-based Q-statistic test and I2 statistics. All statistical analyses were performed using R.3.3.1 software packages (R Foundation for Statistical Computing, Vienna, Austria) and RevMan5.3 (Cochrane Collaboration, Copenhagen, Denmark).Results:Overall, patients with high ERG expression had a worse relapse (OR = 2.5127, 95% CI: 1.5177–4.1601, P = 0.0003) and lower complete remission (OR = 0. 3495, 95% CI: 0.2418–0.5051, P < 0.0001). With regard to the known molecular markers, both internal tandem duplications of the fms-related tyrosine kinase 3 gene (OR = 3.8634, 95% CI: 1.8285–8.1626, P = 0.004) and brain and acute leukemia, cytoplasmic (OR = 3.1538, 95% CI: 2.0537–4.8432, P < 0.0001) were associated with the ERG expression. In addition, the results showed a statistical significance between French-American-British (FAB) classification subtype (minimally differentiated AML and AML without maturation, OR = 4.7902, 95% CI: 2.7772–8.2624, P < 0.0001; acute monocytic leukemia, OR = 0.2324, 95% CI: 0.0899–0.6006, P = 0.0026) and ERG expression.Conclusion:High ERG expression might be used as a strong adverse prognostic factor in CN-AML.

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Section: Discussionsupporting

confidence: 90%

E-26 Transformation-specific Related Gene Expression and Outcomes in Cytogenetically Normal Acute Myeloid Leukemia

Fang

Yuan

Song

et al. 2017

Chinese Medical Journal

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“…In particular, FLT3-internal tandem duplication (ITD) is the most common mutation found in the FLT3 gene (11). It has been reported that patients with AML carrying the FLT3-ITD mutation display a higher peripheral white blood cell (WBC) count, which severely affects the rates of complete remission (CR), relapse (RR) and overall survival (OS) (12). FLT3-ITD mutation eliminates the autoinhibition of FLT3, resulting in the activation of downstream proliferative signaling pathways affecting the proliferation of cells carrying FLT3 mutations n patients with AML (13).…”

Section: Introductionmentioning

confidence: 99%

Association between increased mutation rates in DNMT3Α and FLT3‑ITD and poor prognosis of patients with acute myeloid leukemia

Zhang

Cao

et al. 2019

Exp Ther Med

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A total of 133 patients with acute myeloid leukemia (AML) were enrolled in the current study and were subdivided into 4 groups: 34 harboring DNA methyltransferase 3 α (DNMT3A) + fms related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations, 37 harboring only FLT3-ITD mutation, 32 harboring only DNMT3A mutation and 30 harboring no mutations in DNMT3A and FLT3-ITD (control). Patients in all groups were administered daunorubicin and cytarabine chemotherapy regimens. The rates of complete remission (CR), 1-year relapse (RR) and 3-year overall survival (OS) were compared. Patients in the DNMT3A + FLT3-ITD mutation group exhibited higher proportions of peripheral white blood cells (WBCs) and myeloid progenitor cells compared with those in DNMT3A mutation only, FLT3-ITD mutation only and control groups (P<0.05). The rates of CD15 + and HLA-DR + in the DNMT3A + FLT3-ITD mutation and DNMT3A mutation only groups were significantly higher than those in the FLT3-ITD mutation only and control groups (P<0.05); in addition, the rate of CD38 + in the DNMT3A + FLT3-ITD mutation and FLT3-ITD mutation only groups was significantly higher compared with that in the DNMT3A mutation only and control groups (P<0.05). The overall chemotherapy effectiveness rate, CR, 1-year RR and the 3-year OS rates of patients in the DNMT3A + FLT3-ITD mutation group were significantly worse compared with FLT3-ITD mutation only, DNMT3A mutation only and control groups (P<0.05). The results of this study indicated that increased mutation rates in DNMT3Α and FLT3-ITD may be associated with increased WBC and myeloid progenitor cell counts, an inferior chemotherapy efficacy and prognosis, a lower CR rate, and higher 1-year RR and mortality rate.

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“…Patients with AML and intermediate or normal karyotype and FLT3-ITD faced particularly poor outcomes in our previous study 12 and other studies, [19][20][21] even after allo-HSCT, [22][23][24] unless graft-versus-host disease with graft-versus-leukemia effect occured or sorafenib was added as a maintenance therapy following allo-HSCT. 20 OS.…”

Section: Discussionmentioning

confidence: 82%

“…Patients with AML and intermediate or normal karyotype and FLT3 ‐ITD faced particularly poor outcomes in our previous study and other studies, even after allo‐HSCT, unless graft‐versus‐host disease with graft‐versus‐leukemia effect occured or sorafenib was added as a maintenance therapy following allo‐HSCT . Of course, it is important to identify more prognostic factors which could adapt the most effective therapies to reduce the risk of relapse and improve DFS and OS in this group of patients.…”

Section: Discussionmentioning

confidence: 87%

BCRP mRNA and FLT3‐ITD are independent poor risk factors in adult patients with acute myeloid leukemia and intermediate or normal karyotype

Nasiłowska-Adamska

Warzocha

Solarska

et al. 2017

European J of Haematology

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Outcome of FLT3-ITD-positive acute myeloid leukemia: impact of allogeneic stem cell transplantation and tyrosine kinase inhibitor treatment

Cited by 19 publications

References 43 publications

E-26 Transformation-specific Related Gene Expression and Outcomes in Cytogenetically Normal Acute Myeloid Leukemia

E-26 Transformation-specific Related Gene Expression and Outcomes in Cytogenetically Normal Acute Myeloid Leukemia

Association between increased mutation rates in DNMT3Α and FLT3‑ITD and poor prognosis of patients with acute myeloid leukemia

BCRP mRNA and FLT3‐ITD are independent poor risk factors in adult patients with acute myeloid leukemia and intermediate or normal karyotype

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