Interactive diagnostics in the indication to allogeneic SCT in AML

Abstract

Owing to the heterogeneity of AML, the indication for allogeneic SCT (allo-SCT) requires an exact definition of the individual subentity and risk category. A comprehensive diagnostic approach is needed, which combines cytomorphology, cytogenetics, FISH, molecular genetics and immunophenotyping. Whereas the categorization in three prognostic karyotype groups is well established, rare recurrent aberrations as the unfavorable t(8;16)(p11;p13), inv(3)(q21q26) and t(6;9)(p23;q34) must also be considered. In normal karyotype, PCR analyses reveal prognostically relevant mutations in 485% of cases, and a molecular data set composed of the FLT3-ITD, MLL-PTD, NPM1 and CEBPA mutations was found able to guide the selection of patients for allo-SCT. Some novel markers as the WT1 mutations might further contribute to risk stratification in normal karyotype. The panel of minimal residual disease parameters is being expanded at this time, for example, by quantitative PCR for the NPM1 mutations. Immunophenotyping allows the definition of leukemia-associated phenotypes in nearly all cases, but its position in the indication to allo-SCT has to be validated. Thus, the optimization of the indication to allo-SCT is an ongoing process that should remain in continuous interaction with the increasing panel of known genetic markers and diagnostic methods.

Influence of molecular subgroups on outcome of acute myeloid leukemia with normal karyotype in 141 patients undergoing salvage allogeneic stem cell transplantation in primary induction failure or beyond first relapse

“…[26][27][28] FLT3-ITD is less stable and is more difficult to monitor, but de novo acquisition at a later stage is rare. 26,29,30 Second, the mutant/wild-type ratio and the FLT3-ITD insertion site were not systematically determined. Both parameters have been shown to influence outcome after conventional chemotherapy and alloHSCT in CR1.…”

Early allo-SCT for AML with a complex aberrant karyotype—results from a prospective pilot study

“…Due to a significant survival benefit in comparison with the conventional chemotherapy, allogeneic haematopoietic SCT (HSCT) using matched related-or unrelated-donors is the recommended treatment in CK-AML and other unfavourable karyotypes. [4][5][6][7] However, even after standard related HSCT in CR1, unfavourable cytogenetics at diagnosis predicted an inferior outcome. 8,9 In contrast, cytogenetics had less influence after HSCT from matched unrelated donors, arguing for a stronger GvL effect in the unrelated setting.…”

Allo-SCT for high-risk AML-CR1 in the molecular era: impact of FLT3/ITD outweighs the conventional markers

“…Similarly, the prognostic significance of FLT3/ITD mutation compared with other conventional prognostic markers such as age, white blood cell count, karyotype in patients receiving allo-SCT in AML-CR1 is unknown. 2,11 Here, we report the outcome of allo-SCT in our patients with AML-CR1 with FLT3/ITD in the molecular era. We also compared the impact of conventional prognostic markers in patients with FLT3/ITD þ disease on transplant outcome.…”