Korean J Hematol.  2010 Sep;45(3):177-182. 10.5045/kjh.2010.45.3.177.

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

• Shim H
• Chi HS
• Jang S
• Seo EJ
• Park CJ
• Lee JH
• Lee JH
• Lee KH

• KMID: 2252059
• DOI: http://doi.org/10.5045/kjh.2010.45.3.177

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.

Keyword

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

MeSH Terms

Bone Marrow
Breast
Breast Neoplasms
Disease-Free Survival
Humans
Incidence
Korea
Leukemia
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Retrospective Studies
Tertiary Care Centers
Topoisomerase Inhibitors
World Health Organization
Topoisomerase Inhibitors

Figure

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  Fig. 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.

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  Fig. 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.

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  Fig. 3 Event-free survival plot of 11q23 group vs. non-11q23 group, showing significantly poorer survival of the 11q23 translocated group (P=0.043).

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