Evaluation of prognostic factors in patients with therapy-related acute myeloid leukemia

Sang Hyuk Park; Hyun-Sook Chi; Young-Uk Cho; Seongsoo Jang; Chan-Jeoung Park

doi:10.5045/br.2013.48.3.185

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Original Article

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Blood Res 2013; 48(3):

Published online September 25, 2013

https://doi.org/10.5045/br.2013.48.3.185

Evaluation of prognostic factors in patients with therapy-related acute myeloid leukemia

Sang Hyuk Park, Hyun-Sook Chi^*, Young-Uk Cho, Seongsoo Jang, and Chan-Jeoung Park

Author Info. +

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

Correspondence to : Correspondence to Hyun-Sook Chi, M.D., Ph.D. Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-4502, Fax: +82-2-478-0884, hschi@amc.seoul.kr

Received: May 17, 2013; Revised: July 1, 2013; Accepted: July 12, 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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Abstract

Background

Therapy-related AML (t-AML) occurs as a late complication of chemotherapy administered to treat a prior disorder. Prognostic factors affecting the clinical outcome in t-AML have not yet been clearly defined; therefore, we evaluated these factors in this study.

Methods

Forty-eight patients diagnosed with t-AML within the past 10 years were enrolled, and their chemotherapy regimens categorized into 4 groups: alkylating agents (AK) only, topoisomerase II inhibitors (TI) and AK, TI only, and others. The prognostic factors affecting clinical outcome were evaluated.

Results

Five (10.4%), 21 (43.8%), 9 (18.8%), and 13 (27.0%) patients were treated with AK only, AK and TI, TI only, and others, respectively. Patients with an AML M3 phenotype showed significantly longer overall survival (OS; 55.1 vs. 14.3 months, P=0.040) and disease-free survival (DFS; 61.2 vs. 17.5 months, P=0.049) than other phenotypes. In contrast, patients with a complex karyotype showed significantly shorter OS (7.9 vs. 31.3 months, P=0.008) and DFS (9.5 vs. 38.6 months, P=0.046); additionally, patients with chromosome 5 or 7 abnormalities showed significantly shorter OS (9.1 vs. 30.7 months, P=0.011) than other phenotypes. Only the presence of a complex karyotype or AML M3 phenotype retained prognostic impact in a multivariate analysis.

Conclusion

Only the AML M3 phenotype was identified as having a good prognosis, and this might suggest that it exhibits unique clinical features in t-AML patients. Moreover, our findings indicated that karyotype was the strongest prognostic indicator and predicted a poor prognosis for t-AML patients with a complex karyotype.

Keywords Prognosis, Therapy, Related, AML

Article

Original Article

Blood Res 2013; 48(3): 185-192

Published online September 25, 2013 https://doi.org/10.5045/br.2013.48.3.185

Evaluation of prognostic factors in patients with therapy-related acute myeloid leukemia

Sang Hyuk Park, Hyun-Sook Chi^*, Young-Uk Cho, Seongsoo Jang, and Chan-Jeoung Park

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

Correspondence to: Correspondence to Hyun-Sook Chi, M.D., Ph.D. Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-4502, Fax: +82-2-478-0884, hschi@amc.seoul.kr

Received: May 17, 2013; Revised: July 1, 2013; Accepted: July 12, 2013

Abstract

Background

Methods

Results

Conclusion

Keywords: Prognosis, Therapy, Related, AML

Abstract

Fig 1.

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Figure 1.

The overall survival (A) and disease-free survival (B) of patients with therapy-related AML. Patients were categorized into 4 chemotherapeutic regimen groups for the treatment a primary neoplastic disorder: alkylating agents (AK) only, topoisomerase II inhibitors (TI) and AK, TI only, and others.

Blood Research 2013; 48: 185-192https://doi.org/10.5045/br.2013.48.3.185

Fig 2.

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Figure 2.

The overall survival (A) and disease-free survival (B) of patients with therapy-related AML according to the presence of chromosome 5 or 7 abnormalities at diagnosis.

Blood Research 2013; 48: 185-192https://doi.org/10.5045/br.2013.48.3.185

Fig 3.

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Figure 3.

The overall survival (A) and disease-free survival (B) of patients with therapy-related AML according to the presence of a complex karyotype at diagnosis.

Blood Research 2013; 48: 185-192https://doi.org/10.5045/br.2013.48.3.185

Fig 4.

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Figure 4.

The overall survival (A) and disease-free survival (B) of patients with therapy-related AML according to the presence of the FAB M3 phenotype at diagnosis.

Blood Research 2013; 48: 185-192https://doi.org/10.5045/br.2013.48.3.185

Table 1 . Distribution of primary neoplastic disorders in enrolled patients..

^a)Other disorders include (1 patient each): esophageal cancer, cholangiocarcinoma, non-small cell lung cancer, malignant germinoma, medulloblastoma, ovarian cancer, prostate cancer, thyroid cancer, Ewing's sarcoma, high grade ependymoma, and renal cell carcinoma..

Table 2 . Comparison of clinical presentation with respect to chemotherapeutic regimen..

P value was calculated from the ^a)Chi-square test and ^b)Kruskal-Wallis test..

Abbreviations: AK, alkylating agent; TI, topoisomerase II inhibitor; FAB, French-American-British; PLT, platelet; BM, bone marrow; FLT3 ITD, fms-related tyrosine kinase 3 gene internal tandem duplications; Ch, chromosome; CR, complete remission; SCT, stem cell transplantation..

Table 3 . Comparison of overall and disease free survival..

^a)The median value of BM blast percentage (61.1%, N=48) was used as a cutoff for the determination of the 2 groups. ^b)Comparison of the overall and disease free survival was constructed using the Kaplan-Meier method and P values were obtained from a log-rank test..

Abbreviations: AK, alkylating agent; TI, topoisomerase II inhibitor; FAB, French-American-British; BM, bone marrow; Ch, chromosome; SCT, stem cell transplantation; CI, confidence interval..

Table 4 . Multivariate analysis of overall and disease free survival..

^a)The hazard ratio for the allogeneic SCT, FLT3 ITD mutation, FAB M3, chromosome 5 or chromosome 7 abnormality, and complex karyotype represents relative risk for overall and disease free survival in cases with presence of these variables compared to absence..

Abbreviations: HR, hazard ratio; CI, confidence interval; BM, bone marrow; SCT, stem cell transplantation; FLT3 ITD, fms-related tyrosine kinase 3 gene internal tandem duplications; FAB, French-American-British; Ch, chromosome; NS, not significant..