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Factors influencing survival following first relapse in ALL: A Children’s Oncology Group study
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Survival outcomes remain poor for patients with ALL who experience relapse, with a 5-year OS rate of 36% post-relapse.1 While several factors such as age, WBC count, CNS involvement, cytogenetic subtype, and MRD inform risk stratification at diagnosis, similar indicators for post-relapse outcomes in ALL are limited. A retrospective cohort study of 16,115 pediatric, adolescent, and young adult patients with B-ALL, T-ALL, and infant ALL, of whom 12.7% had relapsed, from 12 COG first-line ALL trials, was performed to identify additional risk factors associated with OS post relapse. The results were published in Leukemia by Rheingold et al.1
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Although relapse rates were similar overall between patients with B-ALL (12.5%) and T-ALL (11.2%), relapse was more common in the infant ALL cohort (34.2%). In patients with B-ALL, 48% of relapses occurred at ≥36 months, with 72.5% of these involving the bone marrow. Whereas, in patients with T-ALL, 64.8% of relapses occurred at <18 months, with 47.1% involving the CNS. |
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In patients with B-ALL, MRD ≥0.01% at the end of induction during frontline therapy increased the risk of relapse post-relapse (p < 0.0001). |
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Overall, the 5-year OS rate post relapse was 48.9%; 52.5% in B-ALL, 35.5% in T-ALL, and 21.5% in infant ALL (p < 0.001). Longer time-to-relapse was associated with improved 5-year OS rates (25.8%, 49.5%, and 66.4% for early, intermediate, and late time-to-relapse, respectively, in patients with B-ALL, and 29.8%, 33.3%, and 58%, respectively, in patients with T-ALL). |
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Post-relapse OS was significantly associated with cytogenetic subtype (p < 0.001). Patients with ETV6::RUNX1 or trisomy 4+10 had better post-relapse OS rates of 74.4% and 70.2%, respectively; however, patients with hypodiploidy or KMT2A-r and TCF3::PBX1 had poor post-relapse OS rates of 14.2% and 31.9%, respectively. |
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This large cohort study identified additional risk factors associated with OS post relapse in patients with ALL. The findings will not only help inform future trial designs but also highlight patient subgroups with worse outcomes post-relapse. |
Abbreviations: ALL, acute lymphoblastic leukemia; B-ALL, B-cell acute lymphoblastic leukemia; CNS, central nervous system; COG, Children’s Oncology Group; KMT2A-r, KMT2A rearrangement; MRD, measurable residual disease; OS, overall survival; T-ALL, T-cell acute lymphoblastic leukemia; WBC, white blood cell.
- Rheingold SR, Bhojwani D, Ji L, et al. Determinants of survival after first relapse of acute lymphoblastic leukemia: A Children's Oncology Group study. Leukemia. 2024. Online ahead of print. DOI: 10.1038/s41375-024-02395-4
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