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

Seung Dok Hong, Yeo Kyeoung Kim, Hee Nam Kim, Se Ryeon Lee, Jae Sook Ahn, Deok Hwan Yang, Je Jung Lee, Il Kwon Lee, Myung Geun Shin, Hyeoung Joon Kim

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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. 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.

Original languageEnglish
Pages (from-to)24-30
Number of pages7
JournalKorean Journal of Hematology
Volume46
Issue number1
DOIs
Publication statusPublished - 2011 Mar 1

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Acute Promyelocytic Leukemia
Anthracyclines
Tretinoin
Combination Drug Therapy
Mutation
Leukemia
Survival
Drug Therapy
Idarubicin
Recurrence
Platelet Count

Keywords

  • Acute promyelocytic leukemia
  • FLT3
  • Prognosis

ASJC Scopus subject areas

  • Hematology

Cite this

Treatment outcome of all-trans retinoic acid/anthracycline combination chemotherapy and the prognostic impact of FLT3/ITD mutation in acute promyelocytic leukemia patients. / Hong, Seung Dok; Kim, Yeo Kyeoung; Kim, Hee Nam; Lee, Se Ryeon; Ahn, Jae Sook; Yang, Deok Hwan; Lee, Je Jung; Lee, Il Kwon; Shin, Myung Geun; Kim, Hyeoung Joon.

In: Korean Journal of Hematology, Vol. 46, No. 1, 01.03.2011, p. 24-30.

Research output: Contribution to journalArticle

Hong, Seung Dok ; Kim, Yeo Kyeoung ; Kim, Hee Nam ; Lee, Se Ryeon ; Ahn, Jae Sook ; Yang, Deok Hwan ; Lee, Je Jung ; Lee, Il Kwon ; Shin, Myung Geun ; Kim, Hyeoung Joon. / Treatment outcome of all-trans retinoic acid/anthracycline combination chemotherapy and the prognostic impact of FLT3/ITD mutation in acute promyelocytic leukemia patients. In: Korean Journal of Hematology. 2011 ; Vol. 46, No. 1. pp. 24-30.
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AU - Kim, Yeo Kyeoung

AU - Kim, Hee Nam

AU - Lee, Se Ryeon

AU - Ahn, Jae Sook

AU - Yang, Deok Hwan

AU - Lee, Je Jung

AU - Lee, Il Kwon

AU - Shin, Myung Geun

AU - Kim, Hyeoung Joon

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N2 - 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. 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.

AB - 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. 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.

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