Impact of Allogeneic Stem Cell Transplant on Outcomes of Patients with Acute Myeloid Leukemia Based on NPM1 and FLT3 Mutational Status

Introduction There have been considerable advances in the understanding of molecular markers in acute myeloid leukemia(AML). It is widely accepted that internal tandem duplication (ITD) in the juxta membrane domain of the fms-like tyrosine kinase-3 (FLT3) gene in patients with AML is associated with an increased risk of relapse and reduced overall survival. In several studies, alloSCT performed in first complete remission (CR) from matched-related donors (MRDs) has been shown to result in an improved survival. There is also evidence that alloSCT improves OS in high allelic ratio FLT3-ITD AML and in patients with low allelic ratio FLT3-ITD AML and wild-type nucleophosmin (NPM1) but not in mutated NPM1 with low FLT3 ITD ratio. We wanted to validate these findings in our own cohort. Methods We retrospectively reviewed 723 consecutive patients (>18 years) with newly diagnosed AML treated at Mayo clinic between January 2007 and July 2016. Patients with intermediate-risk cytogenetics and known NPM1 and FLT3 molecular genetics were included in the study (n =198). Patients who had M3 AML, who were lost to follow up and without molecular data were excluded. We analyzed outcomes based on therapy and molecular mutations. Results Baseline characteristics are listed in Table 1. As expected patients receiving alloSCT were younger and a higher proportion received high intensity induction therapy. The majority of patients were transplanted in CR 1 (72%, n=55), Table 2. Median time to transplant was 4.6 months (range 2-64 months). Median follow up for the entire cohort was 62 months. At last follow up 117 (59%) of patients have died. Median OS for the whole cohort was 27 months. OS was longer in patients receiving alloSCT (median OS 87 months vs 16 months for No SCT, p=0.0001)(Figure 1A). This survival advantage remained significant amongst patients achieving CR1 (Figure 1B). Molecular mutations predicted survival based on FLT3 and NMP1 status primarily amongst the non-transplant cohort (Figure 1C). Patients receiving SCT had a similar survival irrespective of molecular mutation profile(Figure 1D). Amongst the FLT3+ cohort, data on subtype and ITD allelic ratio were available in 47 patients (FLT3 ITD low allelic ratio ( Conclusion In our cohort, patients with intermediate risk AML achieving CR1 benefited from alloSCT. The poor prognostic impact of FLT3 mutations in this cohort may be abrogated by alloSCT. The FLT3 mutation burden (allelic ratio) may help further prognosticate this category of patients with intermediate risk AML.