International Journal of Hematology

DOI: 10.1007/s12185-018-2439-x Pages: 91-97

Nationwide survey of therapy-related leukemia in childhood in Japan

1. Kyoto Prefectural University of Medicine, Department of Pediatrics, Graduate School of Medical Science

2. Shiga University of Medical Science, Department of Pediatrics

3. Tokyo Medical and Dental University, Department of Pediatrics and Developmental Biology

4. Kansai Medical University, Department of Pediatrics

5. Saitama Children’s Medical Center, Department of Hematology/Oncology

6. Kyoto Prefectural University of Medicine, Department of Molecular Diagnostics and Therapeutics, Graduate School of Medical Science

7. Kyoto University, Department of Human Health Sciences, Graduate School of Medicine

8. St. Luke’s International Hospital, Department of Pediatrics

9. Ehime Prefectural Central Hospital, Department of Pediatrics

Correspondence to:
Toshihiko Imamura
Tel: 81-75-251-5571
Email: imamura@koto.kpu-m.ac.jp

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Abstract

Therapy-related leukemia (t-leukemia) is associated with dismal prognosis. Published pediatric t-leukemia data are somewhat outdated and may not reflect recent advances in treatment. We report a retrospective nationwide survey of patients diagnosed between 2000 and 2013 in Japan. We identified 43 patients with pediatric t-leukemia; 33 had t-acute myeloid leukemia (t-AML), eight had t-acute lymphoblastic leukemia (t-ALL) and two had t-acute undifferentiated leukemia. Median age at onset and latency were 12 years and 3.8 years, respectively, consistent with previous reports. Of t-AML patients, 63.6% harbored topoisomerase II inhibitor (topo II)-related genetic abnormalities, while only 12.5% of t-ALL patients had such alterations, suggesting that topo II is not key to t-ALL leukemogenesis. The 7-year overall survival (OS) for all 43 patients was 39.2 ± 11.6%. The 5-year OS was 50 ± 20.4% in t-ALL, and 55.2 ± 11.0% in t-AML. Allogeneic hematopoietic cell transplantation (allo-HCT) was associated with superior 5-year OS (HCT(+) vs. HCT(−), 78.8 vs. 12.1%; p < 0.001), and 26 of 32 patients received allo-HCT in complete remission (CR). Only allo-HCT was associated with superior OS on multivariate analysis (HR 0.003, 95% CI 0.0001–0.098; p < 0.001). These findings suggest that allo-HCT in CR improves pediatric t-leukemia outcomes.

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