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Original Article

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Korean J Hematol 2011; 46(2):

Published online June 21, 2011

https://doi.org/10.5045/kjh.2011.46.2.88

© The Korean Society of Hematology

Prognostic significance of the FLT3 ITD mutation in patients with normal-karyotype acute myeloid leukemia in relapse

Sang Hyuk Park1, Hyun-Sook Chi1*, Sook-Kyung Min1, Young-Uk Cho2, Seongsoo Jang1, Chan-Jeoung Park1, Jung-Hee Lee3, Je-Hwan Lee3, Kyoo-Hyung Lee3, Ho-Joon Im4, and Jong-Jin Seo4

Author Info. +

1Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

2Department of Laboratory Medicine, Eulji University School of Medicine, Eulji General Hospital, Seoul, Korea.

3Department of Internal Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

4Department of Pediatrics, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Correspondence to : Correspondence to Hyun-Sook Chi, M.D., Ph.D. Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, 86, Asanbyungwon-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-4502, Fax: +82-2-478-0884, hschi@amc.seoul.kr

Received: March 10, 2011; Revised: April 11, 2011; Accepted: May 17, 2011

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Background

Fms-like tyrosine kinase 3 internal tandem duplication (FLT3 ITD) mutation is related to poor prognosis in normal-karyotype acute myeloid leukemia (AML). However, the prognostic significance of the mutation at relapse has not been adequately investigated. We investigated the prognostic significance of the FLT3 ITD mutation at relapse in normal-karyotype AML patients.

Methods

We analyzed 69 normal-karyotype AML patients, in whom paired bone marrow samples taken at initial diagnosis and subsequent relapse were analyzed for the FLT3 ITD mutation at the Asan Medical Center between 1995 and 2009.

Results

Forty patients showed a persistent wild-type genotype, 11 showed the FLT3 ITD mutation at diagnosis and relapse, and 9 lost and another 9 acquired the mutation at relapse. The mutation status at relapse affected the overall survival (OS), with the mutation group showing shorter OS and survival after relapse than the wild-type group did (P<0.001 and P<0.001, respectively), despite having received more frequent stem cell transplantation after relapse than the wild-type group did. However, no difference was detected in the OS and survival after relapse with regard to the mutation status at diagnosis.

Conclusion

The patients with FLT3 ITD mutation at relapse showed poorer prognoses than those without the mutation. However, mutation status at diagnosis did not affect the outcome. These results suggest that, in normal-karyotype AML patients with relapse, the prognostic significance of FLT3 ITD mutation at relapse is greater than that of the mutation status at diagnosis.

Keywords AML, Prognosis, FLT3 ITD, Relapse, Normal karyotype

Article

Original Article

Korean J Hematol 2011; 46(2): 88-95

Published online June 21, 2011 https://doi.org/10.5045/kjh.2011.46.2.88

Copyright © The Korean Society of Hematology.

Prognostic significance of the FLT3 ITD mutation in patients with normal-karyotype acute myeloid leukemia in relapse

Sang Hyuk Park1, Hyun-Sook Chi1*, Sook-Kyung Min1, Young-Uk Cho2, Seongsoo Jang1, Chan-Jeoung Park1, Jung-Hee Lee3, Je-Hwan Lee3, Kyoo-Hyung Lee3, Ho-Joon Im4, and Jong-Jin Seo4

1Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

2Department of Laboratory Medicine, Eulji University School of Medicine, Eulji General Hospital, Seoul, Korea.

3Department of Internal Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

4Department of Pediatrics, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Correspondence to: Correspondence to Hyun-Sook Chi, M.D., Ph.D. Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, 86, Asanbyungwon-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-4502, Fax: +82-2-478-0884, hschi@amc.seoul.kr

Received: March 10, 2011; Revised: April 11, 2011; Accepted: May 17, 2011

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Fms-like tyrosine kinase 3 internal tandem duplication (FLT3 ITD) mutation is related to poor prognosis in normal-karyotype acute myeloid leukemia (AML). However, the prognostic significance of the mutation at relapse has not been adequately investigated. We investigated the prognostic significance of the FLT3 ITD mutation at relapse in normal-karyotype AML patients.

Methods

We analyzed 69 normal-karyotype AML patients, in whom paired bone marrow samples taken at initial diagnosis and subsequent relapse were analyzed for the FLT3 ITD mutation at the Asan Medical Center between 1995 and 2009.

Results

Forty patients showed a persistent wild-type genotype, 11 showed the FLT3 ITD mutation at diagnosis and relapse, and 9 lost and another 9 acquired the mutation at relapse. The mutation status at relapse affected the overall survival (OS), with the mutation group showing shorter OS and survival after relapse than the wild-type group did (P<0.001 and P<0.001, respectively), despite having received more frequent stem cell transplantation after relapse than the wild-type group did. However, no difference was detected in the OS and survival after relapse with regard to the mutation status at diagnosis.

Conclusion

The patients with FLT3 ITD mutation at relapse showed poorer prognoses than those without the mutation. However, mutation status at diagnosis did not affect the outcome. These results suggest that, in normal-karyotype AML patients with relapse, the prognostic significance of FLT3 ITD mutation at relapse is greater than that of the mutation status at diagnosis.

Keywords: AML, Prognosis, FLT3 ITD, Relapse, Normal karyotype

Fig 1.

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Figure 1.

Comparison of overall survival (A) and survival after relapse (B) between patients positive and negative for FLT3 ITD mutation at diagnosis.

Blood Research 2011; 46: 88-95https://doi.org/10.5045/kjh.2011.46.2.88

Fig 2.

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Figure 2.

Comparison of overall survival (A) and survival after relapse (B) between patients positive and negative for FLT3 ITD mutation at relapse.

Blood Research 2011; 46: 88-95https://doi.org/10.5045/kjh.2011.46.2.88

Table 1 . Comparison of clinical variables between patients with different paired FLT3 ITD mutation status..

Abbreviations: FAB, French-American-British classification; CR, complete remission; FLT3 ITD, fms-like tyrosine kinase3 internal tandem duplication; NN, negative at diagnosis and relapse; PN, positive at diagnosis and negative at relapse; NP, negative at diagnosis and positive at relapse; PP, positive at diagnosis and relapse; ns, not significant; Hb, hemoglobin; WBC, white blood cell; PLT, platelet; PB, peripheral blood; BM, bone marrow; SCT, stem cell transplantation; NPM1, nucleophosmin..

Table 2 . Comparison of prognosis between patients with different paired FLT3 ITD mutation status..

Abbreviations: CR, complete remission; FLT3 ITD, fms-like tyrosine kinase3 internal tandem duplication; NN, negative at diagnosis and relapse; PN, positive at diagnosis and negative at relapse; NP, negative at diagnosis and positive at relapse; PP, positive at diagnosis and relapse; ns, not significant..

Table 3 . Comparison of clinical variables and prognosis between groups with different FLT3 ITD mutation status at diagnosis and relapse..

Abbreviations: CR, complete remission; Hb, hemoglobin; WBC, white blood cell; PLT, platelet; PB, peripheral blood; BM, bone marrow; SCT, stem cell transplantation; FLT3 ITD, fms-like tyrosine kinase3 internal tandem duplication; NN, negative at diagnosis and relapse; PN, positive at diagnosis and negative at relapse; NP, negative at diagnosis and positive at relapse; PP, positive at diagnosis and relapse; ns, not significant..

Table 4 . Multivariate analysis of OS and survival after relapse with respect to FLT3 ITD mutation status at diagnosis and relapse..

a)P-value was adjusted for WBC count, duration of CR, blast percentage in PB and BM at diagnosis, and SCT performance rates after 1st relapse, b)P-value was adjusted for WBC count and blast percentage in PB and BM at diagnosis..

Abbreviations: HR, hazard ratio; FLT3 ITD, fms-like tyrosine kinase3 internal tandem duplication; ns, not significant; CI, confidence interval..
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