open access publication

Article, 2024

ETV6::RUNX1 Acute Lymphoblastic Leukemia: how much therapy is needed for cure?

Leukemia, ISSN 1476-5551, 0887-6924, Volume 38, 7, Pages 1477-1487, 10.1038/s41375-024-02287-7

Contributors

Østergaard, Anna [1] Fiocco, Marta F 0000-0001-5588-0277 [1] [2] [3] De Groot-Kruseman, Hester A [1] [4] Moorman, Anthony Vincent 0000-0002-9781-6107 [5] [6] Vora, Ajay J 0000-0002-2167-4368 [6] [7] Zimmermann, Martin 0000-0002-0365-3512 [8] [9] Schrappe, Martin 0000-0002-1507-004X [9] [10] Biondi, Andrea 0000-0002-6757-6173 [11] [12] Escherich, Gabriele [13] [14] Stary, Jan 0000-0002-6818-7743 [15] Imai, Chihaya 0000-0001-7435-3464 [16] [17] Imamura, Toshihiko 0000-0002-5727-4470 [18] [19] Heyman, Mats Marshall [20] [21] [22] Schmiegelow, Kjeld [23] [24] Pieters, Rob (Corresponding author) [1] [4]

Affiliations

  1. [1] Princess Máxima Center
    2. [NORA names: Netherlands; Europe, EU; OECD];
  2. [2] Leiden University
    3. [NORA names: Netherlands; Europe, EU; OECD];
  3. [3] Leiden University Medical Center
    4. [NORA names: Netherlands; Europe, EU; OECD];
  4. [4] Dutch Childhood Oncology Group (DCOG), Utrecht, The Netherlands
    5. [NORA names: Netherlands; Europe, EU; OECD];
  5. [5] Newcastle University
    6. [NORA names: United Kingdom; Europe, Non-EU; OECD];

Abstract

Recent trials show 5-year survival rates >95% for ETV6::RUNX1 Acute Lymphoblastic Leukemia (ALL). Since treatment has many side effects, an overview of cumulative drug doses and intensities between eight international trials is presented to characterize therapy needed for cure. A meta-analysis was performed as a comprehensive summary of survival outcomes at 5 and 10 years. For drug dose comparison in non-high risk trial arms, risk group distribution was applied to split the trials into two groups: trial group A with ~70% (range: 63.5–75%) of patients in low risk (LR) (CCLSG ALL2004, CoALL 07-03, NOPHO ALL2008, UKALL2003) and trial group B with ~45% (range: 38.7–52.7%) in LR (AIEOP-BFM ALL 2000, ALL-IC BFM ALL 2002, DCOG ALL10, JACLS ALL-02). Meta-analysis did not show evidence of heterogeneity between studies in trial group A LR and medium risk (MR) despite differences in treatment intensity. Statistical heterogeneity was present in trial group B LR and MR. Trials using higher cumulative dose and intensity of asparaginase and pulses of glucocorticoids and vincristine showed better 5-year event-free survival but similar overall survival. Based on similar outcomes between trials despite differences in therapy intensity, future trials should investigate, to what extent de-escalation is feasible for ETV6::RUNX1 ALL.

Keywords

A-LR, MR, acute lymphoblastic leukemia, arm, asparaginase, comparison, comprehensive summary, cumulative dose, cumulative drug dose, cure, de-escalation, distribution, dose, dose comparison, drug, drug dose, effect, event-free survival, evidence, evidence of heterogeneity, glucocorticoid, group, group A, group B, group distribution, heterogeneity, intensity, international trials, leukemia, low risk, lymphoblastic leukemia, meta-analysis, outcomes, overall survival, overview, patients, pulse, pulse of glucocorticoids, rate, risk, risk group distribution, side, side effects, statistical heterogeneity, study, summary, survival, survival outcomes, survival rate, therapy, therapy intensity, treatment, treatment intensity, trial arms, trial group A, trials, vincristine, years

Funders

  • Danish Cancer Society
  • German Cancer Aid

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