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| ==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)== | | ==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)== |
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− | Differences in expression levels [measured using the FLT3-ITD-to-wild-type (WT) allelic ratio] have prognostic implications [3,7,8,9]. It is commonly agreed that a high FLT3-ITD-to-wild-type allelic ratio is a negative prognostic factor (regardless of cytogenetics); the 2017 European Leukemia Net (ELN) guidelines defined 0.5 as the cut-off between low and high allelic ratios [10]. ''FLT3''-ITD remains relevant as a prognostic factor even after intensive chemotherapy and/or stem cell transplant [3]. ''FLT3'' testing was historically viewed as being purely prognostic; however, with the advent of ''FLT3'' inhibitors, it will likely be considered as both prognostic (clinical outcome) and predictive (treatment benefit) [3]. | + | * Differences in expression levels [measured using the FLT3-ITD-to-wild-type (WT) allelic ratio] have prognostic implications [3,7,8,9]. It is commonly agreed that a high FLT3-ITD-to-wild-type allelic ratio is a negative prognostic factor (regardless of cytogenetics); the 2017 European Leukemia Net (ELN) guidelines defined 0.5 as the cut-off between low and high allelic ratios [10]. ''FLT3''-ITD remains relevant as a prognostic factor even after intensive chemotherapy and/or stem cell transplant [3]. ''FLT3'' testing was historically viewed as being purely prognostic; however, with the advent of ''FLT3'' inhibitors, it will likely be considered as both prognostic (clinical outcome) and predictive (treatment benefit) [3]. |
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− | Allogeneic hematopoietic stem cell transplant (alloHSCT) is generally recommended for patients with ''FLT3''-ITD mutations in first complete remission (CR1), provided they are eligible for transplant therapy and have a suitable donor. Among patients with ''FL3''-ITD mutations in ''CR1'', those who undergo alloHSCT have significantly better outcomes (e.g., prolonged survival and decreased risk of relapse) than those who receive chemotherapy alone. Despite this, ''FLT3''-ITD remains a poor prognostic factor (high relapse rate and short relapse-free and overall survival) after alloHSCT and chemotherapy. Patients with ''FLT3''-ITD AML may benefit from the use of ''FLT3'' tyrosine kinase inhibitors as maintenance therapy to prevent relapse following alloHSCT. | + | * Allogeneic hematopoietic stem cell transplant (alloHSCT) is generally recommended for patients with ''FLT3''-ITD mutations in first complete remission (CR1), provided they are eligible for transplant therapy and have a suitable donor. Among patients with ''FL3''-ITD mutations in ''CR1'', those who undergo alloHSCT have significantly better outcomes (e.g., prolonged survival and decreased risk of relapse) than those who receive chemotherapy alone. Despite this, ''FLT3''-ITD remains a poor prognostic factor (high relapse rate and short relapse-free and overall survival) after alloHSCT and chemotherapy. Patients with ''FLT3''-ITD AML may benefit from the use of ''FLT3'' tyrosine kinase inhibitors as maintenance therapy to prevent relapse following alloHSCT. |
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− | The prognosis for patients with ''FLT3'' mutations can be affected by the presence or absence of additional mutations. Patients who are ''FLT3''-ITD negative (''FLT3''-ITD-) or ''FLT3''-ITD low and positive for nucleophosmin 1 mutations (NPM1+) have a “favorable” prognosis; patients who are FLT3-ITD- (or FLT3-ITDlow) with NPM1-WT have an intermediate prognosis [10]. On the other hand, patients who are FLT3-ITDhigh with NPM1-WT have a “poor” prognosis and are less likely to achieve complete remission (CR) with induction chemotherapy than patients with other ''FLT3''/''NPM1'' combinations [3,13]. | + | * The prognosis for patients with ''FLT3'' mutations can be affected by the presence or absence of additional mutations. Patients who are ''FLT3''-ITD negative (''FLT3''-ITD-) or ''FLT3''-ITD low and positive for nucleophosmin 1 mutations (NPM1+) have a “favorable” prognosis; patients who are FLT3-ITD- (or FLT3-ITDlow) with NPM1-WT have an intermediate prognosis [10]. On the other hand, patients who are FLT3-ITDhigh with NPM1-WT have a “poor” prognosis and are less likely to achieve complete remission (CR) with induction chemotherapy than patients with other ''FLT3''/''NPM1'' combinations [3,13]. |
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− | Given its prognostic and predictive values, it is argued that ''FLT3'' testing should be performed in all AMLs regardless of cytogenetics [3]. If the ''FLT3''-ITD-to-WT allelic ratio is used for risk stratification, harmonisation of ''FLT3'' testing is essential to ensure that comparable results are achieved [3]. | + | * Given its prognostic and predictive values, it is argued that ''FLT3'' testing should be performed in all AMLs regardless of cytogenetics [3]. If the ''FLT3''-ITD-to-WT allelic ratio is used for risk stratification, harmonisation of ''FLT3'' testing is essential to ensure that comparable results are achieved [3]. |
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| ==Familial Forms== | | ==Familial Forms== |