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Original Article

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Blood Res 2013; 48(1):

Published online March 31, 2013

https://doi.org/10.5045/br.2013.48.1.24

© The Korean Society of Hematology

Karyotypic change between diagnosis and relapse as a predictor of salvage therapy outcome in AML patients

Yundeok Kim, Jieun Jang, Shin Yong Hyun, Dohyu Hwang, Soo Jeong Kim, Jin Seok Kim, Jun-Won Cheong, and Yoo Hong Min*

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Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Correspondence to : Correspondence to Yoo Hong Min, M.D., Ph.D. Department of Internal Medicine, Yonsei University College of Medicine, 250, Seongsan-ro, Seodaemun-gu, Seoul 120-752, Korea. Tel: +82-2-2228-1956, Fax: +82-2-362-1253, minbrmmd@yuhs.ac

Received: August 2, 2012; Revised: December 20, 2012; Accepted: February 13, 2013

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

Only a few patients who experience AML relapse derive lasting benefit from re-induction therapy. The utility of reassessing the disease karyotype at relapse is unclear. The main goals of this study were to identify prognostic factors for AML relapse and to determine the prognostic utility of karyotypic change between diagnosis and relapse as a variable for predicting response to salvage therapy for relapsed AML.

Methods

This retrospective study included 58 patients with relapsed AML treated at the Yonsei University College of Medicine between 2005 and 2010. Karyotypes at both diagnosis and relapse were available for 45 patients (77%). A change in karyotype at relapse was observed in 17 of 45 cases (37%), and no change was noted in 28 of 45 cases (62%).

Results

Karyotypic changes between diagnosis and relapse were associated with the response rate (RR) to salvage therapy (P=0.016). Overall survival (OS) and event-free survival (EFS) in the group with karyotypic changes between diagnosis and relapse were significantly different from those with no karyotypic changes (P=0.004 and P=0.010, respectively). We applied multiple multivariate Cox regression analyses to identify independent prognostic factors for overall response (OR), OS, and EFS. A change in karyotype between diagnosis and relapse was significantly associated with OS (P=0.023; RR=2.655) and EFS (P=0.033; RR=2.831).

Conclusion

Karyotypic changes between the diagnosis and relapse of AML could be used to predict outcomes and tailor clinical and biological therapeutic strategies for relapsed AML patients.

Keywords Karyotype, Prognosis, Salvage therapy, Acute myeloid leukemia

Article

Original Article

Blood Res 2013; 48(1): 24-30

Published online March 31, 2013 https://doi.org/10.5045/br.2013.48.1.24

Copyright © The Korean Society of Hematology.

Karyotypic change between diagnosis and relapse as a predictor of salvage therapy outcome in AML patients

Yundeok Kim, Jieun Jang, Shin Yong Hyun, Dohyu Hwang, Soo Jeong Kim, Jin Seok Kim, Jun-Won Cheong, and Yoo Hong Min*

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Correspondence to: Correspondence to Yoo Hong Min, M.D., Ph.D. Department of Internal Medicine, Yonsei University College of Medicine, 250, Seongsan-ro, Seodaemun-gu, Seoul 120-752, Korea. Tel: +82-2-2228-1956, Fax: +82-2-362-1253, minbrmmd@yuhs.ac

Received: August 2, 2012; Revised: December 20, 2012; Accepted: February 13, 2013

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

Only a few patients who experience AML relapse derive lasting benefit from re-induction therapy. The utility of reassessing the disease karyotype at relapse is unclear. The main goals of this study were to identify prognostic factors for AML relapse and to determine the prognostic utility of karyotypic change between diagnosis and relapse as a variable for predicting response to salvage therapy for relapsed AML.

Methods

This retrospective study included 58 patients with relapsed AML treated at the Yonsei University College of Medicine between 2005 and 2010. Karyotypes at both diagnosis and relapse were available for 45 patients (77%). A change in karyotype at relapse was observed in 17 of 45 cases (37%), and no change was noted in 28 of 45 cases (62%).

Results

Karyotypic changes between diagnosis and relapse were associated with the response rate (RR) to salvage therapy (P=0.016). Overall survival (OS) and event-free survival (EFS) in the group with karyotypic changes between diagnosis and relapse were significantly different from those with no karyotypic changes (P=0.004 and P=0.010, respectively). We applied multiple multivariate Cox regression analyses to identify independent prognostic factors for overall response (OR), OS, and EFS. A change in karyotype between diagnosis and relapse was significantly associated with OS (P=0.023; RR=2.655) and EFS (P=0.033; RR=2.831).

Conclusion

Karyotypic changes between the diagnosis and relapse of AML could be used to predict outcomes and tailor clinical and biological therapeutic strategies for relapsed AML patients.

Keywords: Karyotype, Prognosis, Salvage therapy, Acute myeloid leukemia

Fig 1.

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Figure 1.

(A) OS in AML patients with and without karyotypic change between diagnosis and relapse. The 2 groups (P=0.004) showed significant differences in OS. (B) EFS in AML patients with and without karyotypic change between diagnosis and relapse. Karyotypic change was significantly associated with EFS after relapse (P=0.010). a)Cases with changed karyotypes between diagnosis and relapse; b)Cases without changed karyotypes between diagnosis and relapse. Abbreviations: AML, Acute myeloid leukemia; OS, overall survival; EFS, event-free survival.

Blood Research 2013; 48: 24-30https://doi.org/10.5045/br.2013.48.1.24

Table 1 . Karyotypic change between diagnosis and relapse in AML cases.a).

a)Only cases with karyotypic changes between diagnosis and relapse are shown..

Table 2 . Characteristics of patients according to karyotypic changes between diagnosis and relapse..

a)Cases with changed karyotypes between diagnosis and relapse; b)Cases with unchanged karyotypes between diagnosis and relapse..

Abbreviations: FAB, French-American-British classification; EM, extramedullary; WBC, white blood count; Fav., favorable; Int., intermediate; Unfav., unfavorable; No., number; OR, overall response; CR, complete response; CRp, CR with incomplete platelet recovery; HCT, hematopoietic stem cell transplantation; RFI, relapse-free interval; CR1, first complete response; SD, standard deviation; NS, not significant..

Table 3 . Univariate analysis of potential prognostic factors..

Abbreviations: OR, overall response; OS, overall survival; EFS, event-free survival; CR1, first complete remission; No., number; RFI, relapse-free interval; HCT, hematopoietic stem cell transplantation; NE, not evaluated; NS, not significant..

Table 4 . Comparison of prognostic factors by multivariate analysis..

Abbreviations: OR, overall response; OS, overall survival; EFS, event-free survival; HR, hazard ratio; Fav., favorable; Int., intermediate; Unfav., Unfavorable; HCT, hematopoietic stem cell transplantation..
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