Clinical Implications of the FLT3-ITD Allelic Ratio in Acute Myeloid Leukemia in the Context of an Allogeneic Stem Cell Transplantation

Simple Summary The presence of FLT3-ITD is among the most common molecular aberrations in acute myeloid leukemia (AML). Although patients harboring FLT3-ITD are often consolidated by allogeneic hematopoietic stem cell transplantation (HSCT), little is known about how the FLT3-ITD allelic ratio impacts patient outcomes after HSCT. Here, we analyzed the biological and clinical features of these patients in the context of other risk factors, including the ELN2017 risk and the measurable residual disease status (MRD) at HSCT. Our data shows no survival differences between patients with a high or low FLT3-ITD allelic ratio in the context of an allogeneic HSCT, but highlights the importance of pre-HSCT MRD as a prognostic factor. Although the presence of FLT3-ITD, as well as levels of the FLT3-ITD allelic ratio, have been described as prognostic factors in acute myeloid leukemia (AML), little is known about how the FLT3-ITD allelic ratio impacts patients' outcomes when receiving an allogeneic hematopoietic stem cell transplantation (HSCT). We analyzed 118 patients (median age at diagnosis 58.3, range 14.3-82.3 years) harboring FLT3-ITD, of whom 94 patients were consolidated with an allogeneic HSCT and included in outcome analyses. A high FLT3-ITD allelic ratio was associated with a higher white blood cell count, higher blood and bone marrow blasts, and worse ELN2017 risk at diagnosis. Patients with a high FLT3-ITD allelic ratio more often had NPM1 mutations, while patients with a low allelic ratio more often had FLT3-TKD mutations. Patients with a high FLT3-ITD allelic ratio were less likely to achieve a measurable residual disease (MRD)-negative remission prior to allogeneic HSCT and had a trend for a shorter time to relapse. However, there was no distinct cumulative incidence of relapse, non-relapse mortality, or overall survival according to the FLT3-ITD allelic ratio in transplanted patients. While co-mutated FLT3-TKD was associated with better outcomes, the MRD status at HSCT was the most significant factor for outcomes. While our data indicates that an allogeneic HSCT may mitigate the adverse effect of a high FLT3-ITD allelic ratio, comparative studies are needed to evaluate which FLT3-ITD mutated patients benefit from which consolidation strategy.

Automated summary

The presence and allelic ratio of FLT3-ITD have been recognized as prognostic factors in acute myeloid leukemia (AML), but their impact on patient outcomes after allogeneic hematopoietic stem cell transplantation (HSCT) is not well understood. This study found that the FLT3-ITD allelic ratio did not significantly affect survival in patients undergoing HSCT, but highlighted the importance of pre-HSCT measurable residual disease (MRD) as a prognostic factor.