Vol.:(0123456789) 1 3 International Journal of Hematology https://doi.org/10.1007/s12185-019-02599-w ORIGINAL ARTICLE Discontinuation of L-asparaginase and poor response to prednisolone are associated with poor outcome of ETV6-RUNX1-positive pediatric B-cell precursor acute lymphoblastic leukemia Ikuya Usami 1,2  · Toshihiko Imamura 2,3  · Yoshihiro Takahashi 4  · So‑ichi Suenobu 5  · Daiichiro Hasegawa 6  · Yoshiko Hashii 7  · Takao Deguchi 8  · Tsukasa Hori 9  · Akira Shimada 10  · Koji Kato 11  · Eturou Ito 12  · Akiko Moriya‑Saito 2  · Hirohide Kawasaki 13  · Hiroki Hori 8  · Keiko Yumura‑Yagi 14  · Junichi Hara 15  · Atsushi Sato 16  · Keizo Horibe 2  · Japan Association of Childhood Leukemia Study Group (JACLS) Received: 18 September 2018 / Revised: 28 December 2018 / Accepted: 16 January 2019 © Japanese Society of Hematology 2019 Abstract ETV6-RUNX1-positive B precursor acute lymphoblastic leukemia (B-ALL) is a common subtype of pediatric B-ALL that has shown excellent outcomes in contemporary clinical trials for pediatric B-ALL. Examinations of the possibility of reduc- ing therapeutic intensity may thus be explored. This prospective study examined outcomes in 205 pediatric patients with ETV6-RUNX1-positive B-ALL uniformly treated following the Japan Association of Childhood Leukemia Study Group (JACLS) ALL-02 protocol. The JACLS ALL-02 protocol does not employ minimal residual disease detected by polymerase chain reaction (PCR-MRD)-based risk stratifcation; however, 4-year event-free survival (EFS) and overall survival (OS) were 94.4 ± 1.6 and 97.5 ± 1.1%, respectively. In particular, 92 of 205 (44.9%) patients were successfully treated with a less intensive regimen involving only two cycles of high dose methotrexate and one course of re-induction therapy comprising vincristine, L-asparaginase (L-asp), pirarubicin, and prednisolone. Multivariate analysis revealed that discontinuation of L-asp and poor response to prednisolone was, respectively, associated with poor EFS (HR 6.3; 95% CI 1.3–27.0) and OS (HR 17.5; 95% CI 2.3–130), suggesting that the majority of ETV6-RUNX1-positive B-ALL cases may be cured by a less- intensive chemotherapy regimen if the risk stratifcation system including PCR-MRD monitoring and insufcient use of L-asp is avoided. Keywords Poor prednisolone response · L-asparaginase · ETV6-RUNX1 · Pediatric acute lymphoblastic leukemia * Toshihiko Imamura imamura@koto.kpu-m.ac.jp 1 Department of Pediatric Hematology and Oncology, Hyogo Prefectural Amagasaki General Medical Center, Hyogo, Japan 2 Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan 3 Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan 4 Department of Pediatrics, Aomori Prefectural Central Hospital, Aomori, Japan 5 Division of General Pediatrics and Emergency Medicine, Department of Pediatrics, Oita University, Oita, Japan 6 Department of Hematology/Oncology, Hyogo Prefectural Children’s Hospital, Kobe, Japan 7 Department of Pediatrics, Osaka University, Osaka, Japan 8 Department of Pediatrics, Mie University, Tsu, Japan 9 Department of Pediatrics, Sapporo Medical University of Medicine, Hokkaido, Japan 10 Department of Pediatrics, Okayama University, Okayama, Japan 11 Department of Hematology Oncology, Children’s Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan 12 Department of Pediatrics, Hirosaki University, Hirosaki, Japan 13 Department of Pediatrics, Kansai Medical University, Hirakata, Japan 14 Yumura Clinic, Osaka, Japan 15 Department of Pediatric Hematology/Oncology, Osaka City General Hospital, Osaka, Japan 16 Department of Hematology/Oncology, Miyagi Children’s Hospital, Sendai, Japan