Abstract
In the treatment of childhood acute lymphoblastic leukemia (ALL), excess shortening of maintenance therapy resulted in high relapse rate, as shown by our previous trial, TCCSG L92-13, in which maintenance therapy was terminated at 1 year from initiation of treatment. In this study, we aimed to confirm the long-term outcome of L92-13, and to identify who can or cannot be cured by shorter duration of maintenance therapy. To obtain sentinel cytogenetics information that had been missed before, we performed genetic analysis with genomic microarray and target intron-capture sequencing from diagnostic bone marrow smear. Disease-free survival (DFS) at 10 years from the end of therapy was 66.0±2.8%. Females (n=138) had better DFS (74.6±3.7%) than males (n=142, 57.5±4.2%, P=0.002). Patients with TCF3-PBX1 (n=11) and ETV6-RUNX1 (n=16) had excellent DFS (90.9±8.7% and 93.8±6.1%, respectively), whereas high hyperdiploidy (n=23) was the most unfavorable subgroup, with 56.6±10.3% of DFS. Short duration of therapy can cure more than half of pediatric ALL, especially females, TCF3-PBX1 and ETV6-RUNX1. Our retrospective observations suggest a gender/karyotype inhomogeneity on the impact of brief therapy.
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Acknowledgements
We thank Kaori Itagaki for preparing and refining the protocol data for ALL in the TCCSG. We also thank Ms Masayo Matsumura and Ms Yin Yi (the University of Tokyo) and Ms Maki Nakamura and Ms Hitomi Higashi (Kyoto University) for special technical assistance. We thank Dr Julian Tang of the Department of Education for Clinical Research, National Center for Child Health and Development, for proofreading and editing this manuscript. This study was supported in part by the Japan Society for the Promotion of Science (JSPS) through Grants-in-Aid for Scientific Research (KAKENHI) Grant Numbers 26713037 and 26670492, and by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and development, AMED, Grant Number 15ck0106066h0002. This study was also supported by grants from the Takeda Science Foundation, the Japan Leukemia Research Fund and the Children’s Cancer Association of Japan.
Author contributions
MK, TI, AO and AM contributed to the writing of the manuscript. MK, AM, K Koh, MT and AO designed the study. MK, AM, SI, DT, DH, TO, TI, YA, TA, MO, K Kaizu, K Kato, YT, HG, TT and MT contributed to the data gathering. MS, KY, NK, HU, Y Sato, Y Shiraishi, KC, HT, JT, MS and SO contributed to the data analysis. MK, MS, YK and AM interpreted the data. All authors critically reviewed the manuscript and agreed to submit the paper for publication.
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Kato, M., Ishimaru, S., Seki, M. et al. Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children. Leukemia 31, 580–584 (2017). https://doi.org/10.1038/leu.2016.274
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DOI: https://doi.org/10.1038/leu.2016.274
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