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. 2024 Jun;13(12):e7246.
doi: 10.1002/cam4.7246.

Differential impact of asparaginase discontinuation on outcomes of children with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma

Hisashi Ishida  1 , Toshihiko Imamura  2 , Ryoji Kobayashi  3 , Yoshiko Hashii  4 , Takao Deguchi  5 , Takako Miyamura  6 , Megumi Oda  1 , Masaki Yamamoto  7 , Keiko Okada  8 , Hideki Sano  9 , Katsuyoshi Koh  10 , Yuki Yuza  11 , Kenichiro Watanabe  12 , Noriyuki Nishimura  13 , Tetsuya Takimoto  14 , Akiko Moriya-Saito  15 , Masahiro Sekimizu  16 , Souichi Suenobu  17 , Shosuke Sunami  18 , Keizo Horibe  15
Affiliations

Differential impact of asparaginase discontinuation on outcomes of children with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma

Hisashi Ishida et al. Cancer Med. 2024 Jun.

Abstract

Background: Asparaginase is essential for treating T-cell acute lymphoblastic leukemia (T-ALL). Despite the ongoing debate on whether T-ALL and T-cell lymphoblastic lymphoma (T-LBL) are the same disease entity or two distinct diseases, patients with T-LBL often receive the same or similar treatment protocols as those with T-ALL.

Methods: The outcomes of patients with or without L-asparaginase discontinuation were retrospectively analyzed among four national protocols: Japan Association of Childhood Leukemia Study (JACLS) ALL-02 and ALL-97 for T-ALL and Japanese Pediatric Leukemia/Lymphoma Study Group ALB-NHL03 and JACLS NHL-98 for T-LBL. The hazard ratio (HR) was calculated with the Cox regression model by considering L-asparaginase discontinuation as a time-dependent variable.

Results: In total, 199 patients with T-ALL, and 133 patients with T-LBL were included. L-asparaginase discontinuation compromised event-free survival (EFS) of T-ALL patients (ALL-02: HR 3.32, 95% confidence interval [CI] 1.40-7.90; ALL-97: HR 3.39, 95%CI 1.19-9.67). Conversely, EFS compromise was not detected among T-LBL patients (ALB-NHL03: HR 1.39, 95%CI 0.41-4.68; NHL-98: HR 0.92, 95%CI 0.11-7.60).

Conclusion: The effects of L-asparaginase discontinuation differed between T-ALL and T-LBL. We assume that the differential impact results from (1) the inherent differential response to L-asparaginase between them and/or (2) a less stringent assessment of early treatment response in T-LBL than in T-ALL. Given the poor salvage rate of refractory or relapsed T-ALL and T-LBL, optimization of the frontline therapy is critical, and the current study provides a new suggestion for further treatment modifications. However, larger studies in contemporary intensified treatment protocols are required.

Keywords: T‐cell acute lymphoblastic leukemia; T‐cell lymphoblastic lymphoma; acute pancreatitis; allergy; asparaginase; children.

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Conflict of interest statement

The authors have no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Hazard ratio of L‐asparaginase discontinuation on event‐free survival according to the treatment protocols. CI, confidence interval; L‐Asp, L‐Asparaginase.
FIGURE 2
FIGURE 2
Hazard ratio of L‐asparaginase discontinuation on cumulative incidence of relapse according to the treatment protocols. CI, confidence interval; L‐Asp, L‐Asparaginase.
See this image and copyright information in PMC

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