Prognostic impact of allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia patients with internal tandem duplication of FLT3

Predictive value of pretransplantation molecular minimal residual disease assessment by WT1 gene expression in FLT3-positive acute myeloid leukemia

“…Regarding the role of allo-SCT in FLT3-positive AML patients, several studies, mostly retrospective and/or from registries, showed a clear benefit of allo-SCT in FLT3-mutated patients, especially if the transplantation is performed in first CR [8,11,12,14,26,29,30]. A recent meta-analysis, published in 2015, confirmed the efficacy of allo-SCT in terms of OS, DFS, and relapse rate in FLT3-positive patients compared with patients consolidated with chemotherapy or undergoing autologous transplantation (OR 5 1.55, 95% CI 5 1.33-1.82, p !…”

“…Even though there exists much data supporting allo-SCT in FLT3-positive patients, in this context, it is still necessary to define risk subcategories (with different transplantation efficacy) based on FLT3-related (such as the FLT3 allelic burden) and FLT3-unrelated parameters (such as the presence of other pretransplantation predictive factors) [8,[10][11][12][13][14][15][16].…”

Targeting the FLT3 Mutation in Acute Myeloid Leukaemia

“…In addition, allo HSCT has been shown to improve outcomes in FLT3-ITD AML, particularly in patients with a high allelic ratio. [77][78][79] Nevertheless, recent studies indicate that AML patients with NPM1 mutation and low FLT3-ITD allelic ratio may have a more favourable prognosis and should therefore not routinely be assigned to allo HSCT. 42,43,80 In contrast, an ITD insertion site in the TKD1 remained an unfavourable prognostic factor regardless of the applied therapy.…”

Midostaurin approved for FLT3-mutated AML

“…There is a general consensus that allogeneic transplant, when feasible, is the preferred consolidation treatment of patients with FLT3-ITD mutations, although there is ongoing debate regarding the impact of NPM1 mutations and FLT3-ITD allelic burden on the benefit of transplant. [14][15][16][17][18][19][20][21][22][23][24] Midostaurin (N-benzoyl staurosporine, previously referred to as CGP41251 and PKC412) is an indolocarbazole and a direct derivative of staurosporine, the original "pan-kinase" inhibitor. 25 By no means a pan-kinase inhibitor, midostaurin can certainly be referred to as a multitargeted kinase inhibitor, at least in comparison with some other compounds (Figure 1).…”