FLT3 Internal Tandem Duplication Is Associated with High Relapse Rate and Central Nervous System Involvement in Acute Promyelocytic Leukemia

The internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3/ITD) is now accounted as one of important risk factors for the prognosis in acute myelogenous leukemia (AML) patients with normal karyotype. In all-trans retinoic acid era, acute promyelocytic leukemia (APL) has become the most curative subtype of adult AML, and usually hematopoietic stem cell transplantation is not selected for APL patients in 1^st complete remission (CR) or 2^nd CR without minimal residual disease (MRD) at the polymerase chain-reaction level; however, relapses are still reported to occur in 15–25% of cases after achieving 1^st CR without MRD, and some risk factors are proposed including the difference of breakpoint region of the translocation, and leukocyte count at the onset. The incidence of FLT3/ITD in APL has been reported 17–35%; however, it is still a matter of debate that the presence of FLT3/ITD is associated with poor prognosis in APL patients. Thus, we focused on the incidence, clinical features, and prognostic implications of FLT3/ITD in adult newly diagnosed 17 APL patients (median age of 45 years, range 22–67 years, 11 males and 6 females, and median total leukocyte count (TLC) of 2.0 × 10⁹/L, range 0.4– 156.1 × 10⁹/L). All patients achieved CR. The incidence of the presence of FLT3/ITD was 29.4%. The median TLC was significantly higher in FLT3/ITD positive group (median TLC of 9.4 × 10⁹/L) as compared in the negative group (median TLC of 1.2 × 10⁹/L). Higher LDH level in blood was also observed in FLT3/ITD positive group. The rate of central nerves system (CNS) involvement was significantly higher in FLT3/ITD positive group than that in the negative group (60 % vs. 0%). Relapse rate was also significantly higher in FLT3/ITD group (100 % vs. 0%). These data indicate that the presence of FLT3/ITD is associated with the high relapse rate and CNS involvement in APL patients, and implies one of poor prognostic factors.