Allogeneic Transplantation in First Remission Improves Outcome Irrespective of FLT3-ITD Allelic Ratio in FLT3-ITD positive AML

摘要

Adverse prognosis of internal tandem duplication in the FMS-like tyrosine kinase 3 gene(s) (FLT3-ITD) among AML patients may depend on allelic burden.We compared post-remission therapies of chemotherapy and hematopoietic stem cell transplantation (HSCT) in 169 FLT3-ITDmut intermediate cytogenetic risk AML patients with allelic ratio evaluable at diagnosis who achieved first complete remission (CR1) with induction therapy. To minimize selection bias, the analysis was limited to patients who remained in CR1 for at least 4 months (median time to HSCT) after achieving CR1 and propensity score matching was implemented. Sensitivity analysis including patients who remained in CR1 for at least 3 months was also applied.HSCT in CR1 was associated with longer relapse free and overall survival (RFS and OS) with 3-year estimates of 10% vs. 38% (p<0.001) and 18% and 43% (p<0.001) for chemotherapy and HSCT patients respectively. Multivariate regression models showed that HSCT remained statistically significant with improved RFS and OS independent of FLT3-ITD allelic ratio and NPM1 status. Irrespective of post-remission therapy, relapse remains the main reason of treatment failure with 3-year incidence of 68% vs. 41% in chemotherapy and HSCT patients respectively.Allogeneic HSCT improved disease outcomes compared with chemotherapy after propensity score matching was applied. The improvement observed for RFS (HR=0.55, p=0.09) and OS (HR=0.58, p=0.1) with HSCT as post-remission therapy in patients who remained in CR1 for at least 4 months did not reach statistical significance. However, the sensitivity analyses including patients who remained in CR1 for at least 3 months showed significant improvement for both RFS (HR=0.31, p=0.002) and OS (HR=0.27, p=0.02) after propensity score matching.Our results indicate that HSCT in CR1 AML FLT3-ITDmut patients is associated with a longer RFS and OS. Innovative transplantation approaches to improve relapse incidence are urgently needed.