TY - JOUR
T1 - 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
AU - Japan Association of Childhood Leukemia Study Group (JACLS)
AU - Usami, Ikuya
AU - Imamura, Toshihiko
AU - Takahashi, Yoshihiro
AU - Suenobu, So ichi
AU - Hasegawa, Daiichiro
AU - Hashii, Yoshiko
AU - Deguchi, Takao
AU - Hori, Tsukasa
AU - Shimada, Akira
AU - Kato, Koji
AU - Ito, Eturou
AU - Moriya-Saito, Akiko
AU - Kawasaki, Hirohide
AU - Hori, Hiroki
AU - Yumura-Yagi, Keiko
AU - Hara, Junichi
AU - Sato, Atsushi
AU - Horibe, Keizo
N1 - Funding Information:
The authors thank all patients (and their guardians) who participated in this study. The authors also thank the staff at the OSCR data center for data management and all physicians who registered the patients in the JACLS ALL-02 clinical trial.
PY - 2019/4/5
Y1 - 2019/4/5
N2 - 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 reducing 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 stratification; 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 stratification system including PCR-MRD monitoring and insufficient use of L-asp is avoided.
AB - 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 reducing 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 stratification; 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 stratification system including PCR-MRD monitoring and insufficient use of L-asp is avoided.
KW - ETV6-RUNX1
KW - Pediatric acute lymphoblastic leukemia
KW - Poor prednisolone response
KW - l-asparaginase
UR - http://www.scopus.com/inward/record.url?scp=85060972779&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060972779&partnerID=8YFLogxK
U2 - 10.1007/s12185-019-02599-w
DO - 10.1007/s12185-019-02599-w
M3 - Article
C2 - 30689137
AN - SCOPUS:85060972779
VL - 109
SP - 477
EP - 482
JO - International Journal of Hematology
JF - International Journal of Hematology
SN - 0925-5710
IS - 4
ER -