International Journal of Hematology

, Volume 108, Issue 1, pp 91–97 | Cite as

Nationwide survey of therapy-related leukemia in childhood in Japan

  • Toshihiko Imamura
  • Takashi Taga
  • Masatoshi Takagi
  • Hirohide Kawasaki
  • Katsuyoshi Koh
  • Tomohiko Taki
  • Souichi Adachi
  • Atsushi Manabe
  • Yasushi Ishida
  • On behalf of the Leukemia/Lymphoma Committee
  • Japanese Society of Pediatric Hematology Oncology (JSPHO)
Original Article


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 Published pediatric t-leukemia data are somewhat outdated and may not reflect recent advances in treatment.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.


Therapy-related leukemia Allo-HCT Topoisomerase II inhibitor KMT2A 



The authors would like to thank all of the physicians in JSPHO who participated in this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest. A summary of relevant information will be published with the manuscript.

Supplementary material

12185_2018_2439_MOESM1_ESM.tif (101 kb)
Supplementary Fig. 1 Consort diagram of the current retrospective nation-wide survey. (TIFF 100 kb)
12185_2018_2439_MOESM2_ESM.tif (66 kb)
Supplementary Fig. 2 Comparison of the probability of overall survival in patients according to the type of therapy-related disease. t-ALL, therapy-related acute lymphoblastic leukemia; t-AML, 5 years OS, 5 year overall survival. (TIFF 66 kb)
12185_2018_2439_MOESM3_ESM.tif (61 kb)
Supplementary Fig. 3 Comparison of the probability of overall survival in patients treated with allogeneic hematopoietic cell transplantation or not. HCT, allogeneic hematopoietic cell transplantation; 5 years OS, 5 year overall survival. (TIFF 61 kb)
12185_2018_2439_MOESM4_ESM.docx (37 kb)
Supplementary material 4 (DOCX 36 kb)


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Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  • Toshihiko Imamura
    • 1
  • Takashi Taga
    • 2
  • Masatoshi Takagi
    • 3
  • Hirohide Kawasaki
    • 4
  • Katsuyoshi Koh
    • 5
  • Tomohiko Taki
    • 6
  • Souichi Adachi
    • 7
  • Atsushi Manabe
    • 8
  • Yasushi Ishida
    • 9
  • On behalf of the Leukemia/Lymphoma Committee
  • Japanese Society of Pediatric Hematology Oncology (JSPHO)
  1. 1.Department of Pediatrics, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
  2. 2.Department of PediatricsShiga University of Medical ScienceOtsuJapan
  3. 3.Department of Pediatrics and Developmental BiologyTokyo Medical and Dental UniversityTokyoJapan
  4. 4.Department of PediatricsKansai Medical UniversityHirakataJapan
  5. 5.Department of Hematology/OncologySaitama Children’s Medical CenterSaitamaJapan
  6. 6.Department of Molecular Diagnostics and Therapeutics, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
  7. 7.Department of Human Health Sciences, Graduate School of MedicineKyoto UniversityKyotoJapan
  8. 8.Department of PediatricsSt. Luke’s International HospitalTokyoJapan
  9. 9.Department of PediatricsEhime Prefectural Central HospitalEhimeJapan

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