Therapy-related acute leukemia in breast cancer patients: twelve cases treated with a topoisomerase inhibitor

Hyoeun Shim; Hyun-Sook Chi; Seongsoo Jang; Eul-Ju Seo; Chan-Jeoung Park; Jung-Hee Lee; Je-Hwan Lee; Kyoo-Hyung Lee

doi:10.5045/kjh.2010.45.3.177

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Original Article

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Korean J Hematol 2010; 45(3):

Published online September 30, 2010

https://doi.org/10.5045/kjh.2010.45.3.177

Therapy-related acute leukemia in breast cancer patients: twelve cases treated with a topoisomerase inhibitor

Hyoeun Shim¹, Hyun-Sook Chi^1*, Seongsoo Jang¹, Eul-Ju Seo¹, Chan-Jeoung Park¹, Jung-Hee Lee², Je-Hwan Lee², and Kyoo-Hyung Lee²

Author Info. +

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

²Department of Internal Medicine, 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, 86 Asanbyeongwon-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-4502, Fax: +82-2-478-0884, hschi@amc.seoul.kr

Received: July 23, 2010; Revised: September 13, 2010; Accepted: September 14, 2010

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 myeloid neoplasm (t-MN) is a distinct class of acute myeloid leukemia (AML) in the World Health Organization (WHO) classification. Both AML and acute lymphoblastic leukemia (ALL) may develop after treatment for primary cancer. Topoisomerase inhibitors are commonly used to treat breast cancer patients and are well-known for their effect on leukemogenesis of therapy-related acute leukemias (t-AL).

Methods

We retrospectively evaluated bone marrow test results, chromosomal findings, and clinical characteristics of 12 patients who received topoisomerase inhibitors for breast cancer treatment and later developed acute leukemia.

Results

Fourteen patients (0.2%) developed t-AL after treatment for breast cancer. Topoisomerase inhibitors were administered to 12 patients. Among them, 9 patients (75%, 9/12) were diagnosed with therapy-related AML (t-AML) and 3 patients (25%, 3/12) with therapy-related ALL (t-ALL). Eight patients (67%, 8/12) showed translocation involving 11q23 and 3 different partner genes, 19p13.1 (37.5%, 3/8), 9p22 (37.5%, 3/8), and 4q21 (25%, 2/8). The median interval between completion of chemotherapy for breast cancer and occurrence of t-AL was 25 months. Patients with 11q23 translocation showed markedly poorer event-free survival than the group without involvement of 11q23.

Conclusion

The incidence rate of t-AL after treatment for breast cancer was 0.2% in a tertiary hospital in Korea. Translocation involving the MLL gene was frequently found in t-AL caused by a topoisomerase inhibitor and was related to poor prognosis.

Keywords Therapy-related acute myeloid leukemia, Breast cancer, Topoisomerase inhibitors, 11q23

Article

Original Article

Korean J Hematol 2010; 45(3): 177-182

Published online September 30, 2010 https://doi.org/10.5045/kjh.2010.45.3.177

Therapy-related acute leukemia in breast cancer patients: twelve cases treated with a topoisomerase inhibitor

Hyoeun Shim¹, Hyun-Sook Chi^1*, Seongsoo Jang¹, Eul-Ju Seo¹, Chan-Jeoung Park¹, Jung-Hee Lee², Je-Hwan Lee², and Kyoo-Hyung Lee²

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

²Department of Internal Medicine, 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, 86 Asanbyeongwon-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-4502, Fax: +82-2-478-0884, hschi@amc.seoul.kr

Received: July 23, 2010; Revised: September 13, 2010; Accepted: September 14, 2010

Abstract

Background

Methods

Results

Conclusion

Keywords: Therapy-related acute myeloid leukemia, Breast cancer, Topoisomerase inhibitors, 11q23

Abstract

Fig 1.

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Figure 1.

Mixed lineage AML (Case No. 7). (A) Bone marrow aspirate (Wright-Giemsa, ×1,000), showing 2 distinct populations of blasts. (B) Bone marrow biopsy (H&E, ×400), with heavily infiltrated blasts with extensive myelofibrosis.

Blood Research 2010; 45: 177-182https://doi.org/10.5045/kjh.2010.45.3.177

Fig 2.

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Figure 2.

Therapy-related myeloid neoplasm (Case No. 3). (A) Bone marrow biopsy (H&E, ×400), (B) (H&E, ×1,000), showing "packed marrow" infiltration of myeloid cells of different maturation stages, and scattered myeloblasts.

Blood Research 2010; 45: 177-182https://doi.org/10.5045/kjh.2010.45.3.177

Fig 3.

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Figure 3.

Event-free survival plot of 11q23 group vs. non-11q23 group, showing significantly poorer survival of the 11q23 translocated group (P=0.043).

Blood Research 2010; 45: 177-182https://doi.org/10.5045/kjh.2010.45.3.177

Table 1 . Demographics and laboratory findings of 12 patients..

Abbreviations: A, Admycin (doxorubicin hydrochloride); C, Alkyloxan (cyclophosphamide); F, 5FU (fluorouracil); CIS, Cisplatin; TAC, Taxol (paclitaxel); VCS, vincristine sulfate; RTx, radiation treatment; AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; TdT, terminal deoxynucleotidyl transferase; HLA, human leukocyte antigen..