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ACUTE LYMPHOBLASTIC LEUKEMIA

Treatment completion, asparaginase completion, and oncologic outcomes among children, adolescents and young adults with acute lymphoblastic leukemia treated with DFCI Consortium Protocols

Leukemia volume 38, pages 482–490 (2024)Cite this article

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Abstract

Adolescents and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) face worse outcomes than children. While pediatric-inspired protocols have improved outcomes, the ability of patients to complete these intensive regimens and the reasons for discontinuation are unknown. We analyzed a cohort of 332 AYA patients (aged 15–49 years) and 1159 children (aged 1–14 years) with Ph-negative ALL treated on DFCI consortium protocols. We found that AYA patients completed treatment at lower rates than children (60.8% vs. 89.7%, p < 0.001), primarily due to higher rates of early treatment failure (14.5% vs. 2.4%, p < 0.001). Withdrawal from treatment for toxicity, social/personal, or unknown reasons was uncommon, but higher among AYA patients (9.3% vs 4.7%, p = 0.001). Patients who remained on assigned therapy for one year had favorable overall survival (AYA 5-year OS 88.9%; children 5-year OS 96.4%; p < 0.001). Among patients who continued treatment for 1 year, AYA patients completed asparaginase (defined as receiving 26+ weeks) at lower rates than children (79.1% vs. 89.6%, p < 0.001). Patients who received more weeks of consolidation asparaginase had higher overall and event-free survival. Efforts should focus on identifying patients at risk for early treatment failure and optimizing asparaginase delivery.

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Fig. 1: Schematic representation of patient treatment disposition.
Fig. 2: Long term outcomes of patients who stayed on protocol for at least 1 year.
Fig. 3: Overall survival of patients based on asparaginase completion status.
Fig. 4: Cumulative incidence of relapse with death as competing risk by asparaginase completion status (defined as receiving > 26 weeks of post-induction asparaginase).

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request as long as privacy considerations are maintained.

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Authors and Affiliations

  1. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Yannis K. Valtis

  2. Department of Data Science, Dana Farber Cancer Institute, Boston, MA, USA

    Yael Flamand

  3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Shai Shimony, Martha Wadleigh, Richard M. Stone, Daniel J. DeAngelo & Marlise R. Luskin

  4. Department of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Pediatric Hematology Oncology, Boston Children’s Hospital, Boston, MA, USA

    Andrew E. Place, Lewis B. Silverman, Lynda M. Vrooman & Stephen E. Sallan

  5. Department of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA

    Andrew M. Brunner

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  1. Yannis K. Valtis
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Contributions

YV extracted the data from the charts, designed the data analysis, and drafted the manuscript. SS extracted data from the chart. AP, LS, LV, AB, SS, and MW designed the analysis, and identified patients for inclusion in the cohort. DD conceptualized the study and helped design the analysis. SS and RS provided pediatric and adult expertise respectively in the design of the analysis. ML oversaw the creation of the cohort, the design of the analysis, and the drafting of the manuscript. All authors revised the final manuscript.

Corresponding author

Correspondence to Marlise R. Luskin.

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Competing interests

YV received a consultancy fee from EastRx. LS was on the advisory board of Jazz Pharma, Takeda, Servier, and Syndax. AB received consultancy funding from Acceleron Pharma, Biogen, Celgene/BMS, Forty Seven, Jazz Pharma, Novartis, Takeda, and Xcenda, and research funding from Celgene/BMS, Novartis, Takeda, GSK, Janssen, and Astra Zeneka. DD received consultancy funding from Amgen, Autolos, Agios, Blueprint Medicines Corporation, Forty Seven, Incyte Corporation, Jazz Pharma, Novartis, Pfizer, Shire, and Takeda, and research funding from Bluperint Medicines Corporation, Novartis, Abbvie, and Glycomimetics. MRL received research funding from AbbVie, Novartis and was on advisory boards Pfizer, Novartis.

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Valtis, Y.K., Flamand, Y., Shimony, S. et al. Treatment completion, asparaginase completion, and oncologic outcomes among children, adolescents and young adults with acute lymphoblastic leukemia treated with DFCI Consortium Protocols. Leukemia 38, 482–490 (2024). https://doi.org/10.1038/s41375-023-02115-4

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