Prognostic significance of FLT3 mutations in pediatric non-promyelocytic acute myeloid leukemia

Abstract 

FLT3 is a receptor tyrosine kinase involved in the survival of hematopoietic stem cells, and mutations of FLT3 have been reported to be of prognostic significance. This is the first study of FLT3 mutations in pediatric non-promyelocytic AML patients that received the same treatment scheme in single institute. FLT3 internal tandem duplication of the juxtamembrane domain (FLT3/ITD) and a point mutation in the tyrosine kinase domain (FLT3/TKD) were analyzed in 61 patients by PCR of genomic DNA. The incidence of FLT/ITD and FLT/TKD were 6.6% (4/61) and 3.3% (2/61), respectively. Patients with FLT3/TKD remain alive after autologous stem cell transplantation. The disease-free survival (DFS) of patients with FLT3/ITD (0%) was significantly lower than that of the others (52%). FLT3/ITD was the sole adverse prognostic factor for DFS by multivariate analysis (RR=5.6). Patients with FLT3/ITD relapsed early after complete remission even after receiving bone marrow transplantation from a matched related donor with little BuCy conditioning. New therapeutic scheme such as stem cell transplantation with more intensive conditioning just after complete remission could be applied in pediatric non-promyelocytic AML patients with the FLT3/ITD mutation.

Keywords: FLT3, Internal tandem duplication, Tyrosine kinase domain mutation, Acute myeloid leukemia, Pediatric age