Korean J Hematol.  2011 Mar;46(1):24-30. 10.5045/kjh.2011.46.1.24.

Treatment outcome of all-trans retinoic acid/anthracycline combination chemotherapy and the prognostic impact of FLT3/ITD mutation in acute promyelocytic leukemia patients

• Hong SD
• Kim YK
• Kim HN
• Lee SR
• Ahn JS
• Yang DH
• Lee JJ
• Lee IK
• Shin MG
• Kim HJ

• KMID: 2252015
• DOI: http://doi.org/10.5045/kjh.2011.46.1.24

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/m2/day) and idarubicin (12 mg/m2/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.
CONCLUSION
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.

Keyword

Acute promyelocytic leukemia; FLT3; Prognosis

MeSH Terms

Bone Marrow
Drug Therapy, Combination
Humans
Idarubicin
Leukemia, Promyelocytic, Acute
Lifting
Multivariate Analysis
Platelet Count
Prognosis
Recurrence
Treatment Outcome
Tretinoin
Idarubicin
Tretinoin

Figure

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  Fig. 1 Kaplan-Meier analysis of the APL patients. (A) Overall survival (OS) and (B) leukemia-free survival (LFS).

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  Fig. 2 Kaplan-Meier analysis of APL according to pretreatment risk stratification. (A) Overall survival (OS) and (B) leukemia-free survival (LFS).

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  Fig. 3 Kaplan-Meier analysis of APL patients with the FLT3/ITD mutation (FLT3/ITD+) and without the mutation (FLT3/ITD-). (A) Overall survival (OS) and (B) leukemia-free survival (LFS).

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