Changes

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

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].

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.  

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].  

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].

==Familial Forms==

==Familial Forms==