title: Treatment outcome of all-trans retinoic acid/anthracycline combination chemotherapy and the prognostic impact of FLT3/ITD mutation in acute promyelocytic leukemia patients.
abstract: BACKGROUND
  All-trans retinoic acid (ATRA)/anthracycline chemotherapy is beneficial in newly diagnosed acute promyelocytic leukemia (APL); however, it is important to identify patients with high-risk disease to increase the cure rate. We investigated the outcome of ATRA/anthracycline chemotherapy and clinicobiological correlations of FLT3/ITD and NPM1 mutations in APL patients.
  
  
  METHODS
  Induction therapy included oral ATRA (45 mg/m(2)/day) and idarubicin (12 mg/m(2)/day, intravenous, on days 2, 4, and 6). Patients achieving complete remission (CR) received 3 courses of ATRA combined with reinforced consolidation therapy. Mutations were analyzed using GeneScan and polymerasae chain reaction assays of bone marrow samples obtained from patients at diagnosis.
  
  
  RESULTS
  Forty-five (84.9%) of 53 eligible patients achieved CR. The overall relapse rate was 8.9%, and the 3-year overall survival (OS) and leukemia-free survival (LFS) were 84.9±4.9% and 77.5±6.0%, respectively. The NPM1 mutation was not found in any patient, while the FLT3/ITD mutation was found in 10 (20.0%) patients. Of the FLT3/ITD+ patients, 80% belonged to the high-risk group, defined according to the presenting WBC and platelet counts. Among the patients who achieved CR, those who were FLT3/ITD+ had a higher relapse rate than those FLT3/ITD-. FLT3/ITD+ patients also had a significantly lower 3-year LFS than FLT3/ITD- patients. Multivariate analysis of the LFS showed that the FLT3/ITD mutation was independently associated with a shorter overall LFS, after adjusting for pretreatment risk stratification.
  
  
  CONCLUSIONS
  This study investigated the clinical outcome of newly diagnosed APL patients treated with ATRA/anthracycline chemotherapy. Patients carrying the FLT3/ITD mutation had more aggressive clinical features and a poorer clinical outcome.
authors: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors: Seung-Dok
authors: SD
authors: Hong
authors: Yeo-Kyeoung
authors: YK
authors: Kim
authors: Hee-Nam
authors: HN
authors: Kim
authors: Se Ryeon
authors: SR
authors: Lee
authors: Jae-Sook
authors: JS
authors: Ahn
authors: Deok-Hwan
authors: DH
authors: Yang
authors: Je-Jung
authors: JJ
authors: Lee
authors: Il-Kwon
authors: IK
authors: Lee
authors: Myung-Geun
authors: MG
authors: Shin
authors: Hyeoung-Joon
authors: HJ
authors: Kim