Low incidence of osteonecrosis in childhood acute lymphoblastic leukemia treated with ALL-97 and ALL-02 study of Japan association of childhood leukemia study group

Kenichi Sakamoto, Toshihiko Imamura, Kentaro Kihira, Koji Suzuki, Hisashi Ishida, Hiromi Morita, Miyako Kanno, Takeshi Mori, Hidefumi Hiramatsu, Kousaku Matsubara, Kiminori Terui, Yoshihiro Takahashi, So Ichi Suenobu, Daiichiro Hasegawa, Yoshiyuki Kosaka, Koji Kato, Akiko Moriya-Saito, Atsushi Sato, Hirohide Kawasaki, Keiko Yumura-YagiJunichi Hara, Hiroki Hori, Keizo Horibe

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Abstract

Purpose Osteonecrosis (ON) is a serious complication of the treatment of childhood acute lymphoblastic leukemia (ALL); however, data relating to ON in Asian pediatric patients with ALL are scarce. Therefore, we performed a retrospective analysis of cohorts of Japanese patients with ALL to clarify the incidence, clinical characteristics, and risk factors of ON. Patients and Methods The incidence and characteristics of ON were determined in patients with ALL (n = 1,662) enrolled in two studies from the Japan Association of Childhood Leukemia Study (JACLS) group (n = 635 and n = 1,027 patients treated with the ALL-97 and ALL-02 protocols, respectively). Results In total, 24 of 1,662 patients suffered from ON, of which 12 of 635 and 12 of 1,027 patients were treated with the ALL-97 and the ALL-02 protocol, respectively. Of the 24 patients, 23 were older than 10 years. In multivariate analysis, age ($ 10 years) was the sole significant risk factor for ON (P, .001). Separate evaluation of patients $ 10 years of age indicated a 5-year cumulative incidence of ON of 7.2% (95% CI, 4.0% to 12.6%) and 5.9% (95% CI, 3.3% to 10.4%) in the ALL-97 and the ALL-02 protocol, respectively, which was lower than reported previously, despite an administration of dexamethasone (DEX) similar to that in comparable studies; however, concomitant administration of DEX and L-asparaginase was reduced in the JACLS protocols. Conclusion We identified a low frequency of ON in the JACLS ALL-97 and ALL-02 studies. Although the sole risk factor for ON was age ($ 10 years), even among high-risk patients, ON incidence was significantly lower than that reported in previous studies. These results suggest that, not only the total amount of DEX, but also how DEX and L-asparaginase are administered, which affects the clearance of DEX, may be associated with ON incidence in patients with ALL.

Original languageEnglish
Pages (from-to)900-907
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number9
DOIs
Publication statusPublished - Jan 1 2018

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Osteonecrosis
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Japan
Leukemia
Incidence
Dexamethasone
Asparaginase
Cohort Studies
Multivariate Analysis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Low incidence of osteonecrosis in childhood acute lymphoblastic leukemia treated with ALL-97 and ALL-02 study of Japan association of childhood leukemia study group. / Sakamoto, Kenichi; Imamura, Toshihiko; Kihira, Kentaro; Suzuki, Koji; Ishida, Hisashi; Morita, Hiromi; Kanno, Miyako; Mori, Takeshi; Hiramatsu, Hidefumi; Matsubara, Kousaku; Terui, Kiminori; Takahashi, Yoshihiro; Suenobu, So Ichi; Hasegawa, Daiichiro; Kosaka, Yoshiyuki; Kato, Koji; Moriya-Saito, Akiko; Sato, Atsushi; Kawasaki, Hirohide; Yumura-Yagi, Keiko; Hara, Junichi; Hori, Hiroki; Horibe, Keizo.

In: Journal of Clinical Oncology, Vol. 36, No. 9, 01.01.2018, p. 900-907.

Research output: Contribution to journalArticle

Sakamoto, K, Imamura, T, Kihira, K, Suzuki, K, Ishida, H, Morita, H, Kanno, M, Mori, T, Hiramatsu, H, Matsubara, K, Terui, K, Takahashi, Y, Suenobu, SI, Hasegawa, D, Kosaka, Y, Kato, K, Moriya-Saito, A, Sato, A, Kawasaki, H, Yumura-Yagi, K, Hara, J, Hori, H & Horibe, K 2018, 'Low incidence of osteonecrosis in childhood acute lymphoblastic leukemia treated with ALL-97 and ALL-02 study of Japan association of childhood leukemia study group', Journal of Clinical Oncology, vol. 36, no. 9, pp. 900-907. https://doi.org/10.1200/JCO.2017.75.5066
Sakamoto, Kenichi ; Imamura, Toshihiko ; Kihira, Kentaro ; Suzuki, Koji ; Ishida, Hisashi ; Morita, Hiromi ; Kanno, Miyako ; Mori, Takeshi ; Hiramatsu, Hidefumi ; Matsubara, Kousaku ; Terui, Kiminori ; Takahashi, Yoshihiro ; Suenobu, So Ichi ; Hasegawa, Daiichiro ; Kosaka, Yoshiyuki ; Kato, Koji ; Moriya-Saito, Akiko ; Sato, Atsushi ; Kawasaki, Hirohide ; Yumura-Yagi, Keiko ; Hara, Junichi ; Hori, Hiroki ; Horibe, Keizo. / Low incidence of osteonecrosis in childhood acute lymphoblastic leukemia treated with ALL-97 and ALL-02 study of Japan association of childhood leukemia study group. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 9. pp. 900-907.
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abstract = "Purpose Osteonecrosis (ON) is a serious complication of the treatment of childhood acute lymphoblastic leukemia (ALL); however, data relating to ON in Asian pediatric patients with ALL are scarce. Therefore, we performed a retrospective analysis of cohorts of Japanese patients with ALL to clarify the incidence, clinical characteristics, and risk factors of ON. Patients and Methods The incidence and characteristics of ON were determined in patients with ALL (n = 1,662) enrolled in two studies from the Japan Association of Childhood Leukemia Study (JACLS) group (n = 635 and n = 1,027 patients treated with the ALL-97 and ALL-02 protocols, respectively). Results In total, 24 of 1,662 patients suffered from ON, of which 12 of 635 and 12 of 1,027 patients were treated with the ALL-97 and the ALL-02 protocol, respectively. Of the 24 patients, 23 were older than 10 years. In multivariate analysis, age ($ 10 years) was the sole significant risk factor for ON (P, .001). Separate evaluation of patients $ 10 years of age indicated a 5-year cumulative incidence of ON of 7.2{\%} (95{\%} CI, 4.0{\%} to 12.6{\%}) and 5.9{\%} (95{\%} CI, 3.3{\%} to 10.4{\%}) in the ALL-97 and the ALL-02 protocol, respectively, which was lower than reported previously, despite an administration of dexamethasone (DEX) similar to that in comparable studies; however, concomitant administration of DEX and L-asparaginase was reduced in the JACLS protocols. Conclusion We identified a low frequency of ON in the JACLS ALL-97 and ALL-02 studies. Although the sole risk factor for ON was age ($ 10 years), even among high-risk patients, ON incidence was significantly lower than that reported in previous studies. These results suggest that, not only the total amount of DEX, but also how DEX and L-asparaginase are administered, which affects the clearance of DEX, may be associated with ON incidence in patients with ALL.",
author = "Kenichi Sakamoto and Toshihiko Imamura and Kentaro Kihira and Koji Suzuki and Hisashi Ishida and Hiromi Morita and Miyako Kanno and Takeshi Mori and Hidefumi Hiramatsu and Kousaku Matsubara and Kiminori Terui and Yoshihiro Takahashi and Suenobu, {So Ichi} and Daiichiro Hasegawa and Yoshiyuki Kosaka and Koji Kato and Akiko Moriya-Saito and Atsushi Sato and Hirohide Kawasaki and Keiko Yumura-Yagi and Junichi Hara and Hiroki Hori and Keizo Horibe",
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TY - JOUR

T1 - Low incidence of osteonecrosis in childhood acute lymphoblastic leukemia treated with ALL-97 and ALL-02 study of Japan association of childhood leukemia study group

AU - Sakamoto, Kenichi

AU - Imamura, Toshihiko

AU - Kihira, Kentaro

AU - Suzuki, Koji

AU - Ishida, Hisashi

AU - Morita, Hiromi

AU - Kanno, Miyako

AU - Mori, Takeshi

AU - Hiramatsu, Hidefumi

AU - Matsubara, Kousaku

AU - Terui, Kiminori

AU - Takahashi, Yoshihiro

AU - Suenobu, So Ichi

AU - Hasegawa, Daiichiro

AU - Kosaka, Yoshiyuki

AU - Kato, Koji

AU - Moriya-Saito, Akiko

AU - Sato, Atsushi

AU - Kawasaki, Hirohide

AU - Yumura-Yagi, Keiko

AU - Hara, Junichi

AU - Hori, Hiroki

AU - Horibe, Keizo

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose Osteonecrosis (ON) is a serious complication of the treatment of childhood acute lymphoblastic leukemia (ALL); however, data relating to ON in Asian pediatric patients with ALL are scarce. Therefore, we performed a retrospective analysis of cohorts of Japanese patients with ALL to clarify the incidence, clinical characteristics, and risk factors of ON. Patients and Methods The incidence and characteristics of ON were determined in patients with ALL (n = 1,662) enrolled in two studies from the Japan Association of Childhood Leukemia Study (JACLS) group (n = 635 and n = 1,027 patients treated with the ALL-97 and ALL-02 protocols, respectively). Results In total, 24 of 1,662 patients suffered from ON, of which 12 of 635 and 12 of 1,027 patients were treated with the ALL-97 and the ALL-02 protocol, respectively. Of the 24 patients, 23 were older than 10 years. In multivariate analysis, age ($ 10 years) was the sole significant risk factor for ON (P, .001). Separate evaluation of patients $ 10 years of age indicated a 5-year cumulative incidence of ON of 7.2% (95% CI, 4.0% to 12.6%) and 5.9% (95% CI, 3.3% to 10.4%) in the ALL-97 and the ALL-02 protocol, respectively, which was lower than reported previously, despite an administration of dexamethasone (DEX) similar to that in comparable studies; however, concomitant administration of DEX and L-asparaginase was reduced in the JACLS protocols. Conclusion We identified a low frequency of ON in the JACLS ALL-97 and ALL-02 studies. Although the sole risk factor for ON was age ($ 10 years), even among high-risk patients, ON incidence was significantly lower than that reported in previous studies. These results suggest that, not only the total amount of DEX, but also how DEX and L-asparaginase are administered, which affects the clearance of DEX, may be associated with ON incidence in patients with ALL.

AB - Purpose Osteonecrosis (ON) is a serious complication of the treatment of childhood acute lymphoblastic leukemia (ALL); however, data relating to ON in Asian pediatric patients with ALL are scarce. Therefore, we performed a retrospective analysis of cohorts of Japanese patients with ALL to clarify the incidence, clinical characteristics, and risk factors of ON. Patients and Methods The incidence and characteristics of ON were determined in patients with ALL (n = 1,662) enrolled in two studies from the Japan Association of Childhood Leukemia Study (JACLS) group (n = 635 and n = 1,027 patients treated with the ALL-97 and ALL-02 protocols, respectively). Results In total, 24 of 1,662 patients suffered from ON, of which 12 of 635 and 12 of 1,027 patients were treated with the ALL-97 and the ALL-02 protocol, respectively. Of the 24 patients, 23 were older than 10 years. In multivariate analysis, age ($ 10 years) was the sole significant risk factor for ON (P, .001). Separate evaluation of patients $ 10 years of age indicated a 5-year cumulative incidence of ON of 7.2% (95% CI, 4.0% to 12.6%) and 5.9% (95% CI, 3.3% to 10.4%) in the ALL-97 and the ALL-02 protocol, respectively, which was lower than reported previously, despite an administration of dexamethasone (DEX) similar to that in comparable studies; however, concomitant administration of DEX and L-asparaginase was reduced in the JACLS protocols. Conclusion We identified a low frequency of ON in the JACLS ALL-97 and ALL-02 studies. Although the sole risk factor for ON was age ($ 10 years), even among high-risk patients, ON incidence was significantly lower than that reported in previous studies. These results suggest that, not only the total amount of DEX, but also how DEX and L-asparaginase are administered, which affects the clearance of DEX, may be associated with ON incidence in patients with ALL.

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