Pre-transplant FLT3/ITD status predicts outcome in FLT3-mutated acute myeloid leukemia following allogeneic stem cell transplantation

Abstract

Acute myeloid leukemia (AML) with fetal liver tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is associated with poor prognosis, and allogeneic stem cell transplantation (Allo-SCT) seems to be the preferred therapeutic approach. However, the predictors of post-transplant outcomes were not well-defined. The aim of the study was to evaluate the significance of FLT3/ITD mutation by polymerase chain reaction as minimal residual disease (MRD) marker of outcomes after transplantation. We identified 43 patients (28 females and 15 males) with FLT3-mutated AML at the median age of 45 years who were allografted between 2009 and 2019. Hematological status at transplant was as follows: the first complete remission (CR1) in 29 patients, CR2 in 5, and 9 patients were transplanted in marrow aplasia (MA). Twenty-seven patients were FLT3 MRD negative at transplant. Median time from diagnosis to transplant was 16.7 months. Post-allograft CR rate was 88%. The relapse incidence (RI) was lower for patients who were FLT3 MRD negative at transplant when compared with those with FLT3 MRD positivity (41% vs 59%; p = 0.01). The patients who eradicated FLT3/ITD at day + 30 after transplant had lower RI than those with detectable FLT3/ITD (23% vs 76%; p = <0.001). The 2-year LFS and OS were 53% and 54%, with the median OS and LFS of 28 months and 27 months, respectively. Patients with CR1/2 and FLT3 MRD(−) had a 2-year OS of 80%. The FLT3 MRD negativity at transplant prolonged LFS in multivariate analysis (HR 5.3 95%CI 1.97-14.2); p < 0.001), whereas FLT3 MRD negativity and unrelated donor predicted favorable OS.

MRD Tailored Therapy in AML: What We Have Learned So Far

“…Although FLT3 harbors frequent recurring mutations, the internal tandem duplication ( FLT3/ ITD) is highly unstable and can be gained or lost during therapy ( 24 , 25 ). Some research groups still show its potential as a good prognosticator since the presence of the FLT3/ ITD is a strong indicator of residual disease ( 26 – 28 ). However, FLT3/ ITD negativity does not imply that residual leukemia cells are absent, and therefore highly sensitive techniques will be required to ensure FLT3/ ITD negativity ( 29 , 30 ).…”