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

Japan Association of Childhood Leukemia Study Group (JACLS)

Research output: Contribution to journalArticle

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 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.

Original languageEnglish
JournalInternational Journal of Hematology
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Asparaginase
B-Lymphoid Precursor Cells
Prednisolone
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Pediatrics
Polymerase Chain Reaction
Disease-Free Survival
Japan
Leukemia
Survival
Residual Neoplasm
Vincristine
Methotrexate
Multivariate Analysis
Clinical Trials
Prospective Studies
Drug Therapy
Therapeutics

Keywords

  • ETV6-RUNX1
  • l-asparaginase
  • Pediatric acute lymphoblastic leukemia
  • Poor prednisolone response

ASJC Scopus subject areas

  • Hematology

Cite this

@article{84c1caf8a5c342f1be87ef0d40388811,
title = "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",
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 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.",
keywords = "ETV6-RUNX1, l-asparaginase, Pediatric acute lymphoblastic leukemia, Poor prednisolone response",
author = "{Japan Association of Childhood Leukemia Study Group (JACLS)} and Ikuya Usami and Toshihiko Imamura and Yoshihiro Takahashi and Suenobu, {So ichi} and Daiichiro Hasegawa and Yoshiko Hashii and Takao Deguchi and Tsukasa Hori and Akira Shimada and Koji Kato and Eturou Ito and Akiko Moriya-Saito and Hirohide Kawasaki and Hiroki Hori and Keiko Yumura-Yagi and Junichi Hara and Atsushi Sato and Keizo Horibe",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s12185-019-02599-w",
language = "English",
journal = "International Journal of Hematology",
issn = "0925-5710",
publisher = "Springer Japan",

}

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

PY - 2019/1/1

Y1 - 2019/1/1

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 - l-asparaginase

KW - Pediatric acute lymphoblastic leukemia

KW - Poor prednisolone response

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

JO - International Journal of Hematology

JF - International Journal of Hematology

SN - 0925-5710

ER -