ETV6-RUNX1-positive childhood acute lymphoblastic leukemia

Improved outcome with contemporary therapy

D. Bhojwani, D. Pei, J. T. Sandlund, S. Jeha, R. C. Ribeiro, J. E. Rubnitz, S. C. Raimondi, S. Shurtleff, M. Onciu, C. Cheng, E. Coustan-Smith, W. P. Bowman, Scott Howard, M. L. Metzger, H. Inaba, W. Leung, W. E. Evans, D. Campana, M. V. Relling, C. H. Pui

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Abstract

ETV6-RUNX1 fusion is the most common genetic aberration in childhood acute lymphoblastic leukemia (ALL). To evaluate whether outcomes for this drug-sensitive leukemia are improved by contemporary risk-directed therapy, we studied clinical features, response and adverse events of 168 children with newly diagnosed ETV6-RUNX1-positive ALL on St Jude Total Therapy studies XIIIA (N36), XIIIB (N38) and XV (N94). Results were compared with 494 ETV6-RUNX1-negative B-precursor ALL patients. ETV6-RUNX1 was associated with age 1-9 years, pre-treatment classification as low risk and lower levels of minimal residual disease (MRD) on day 19 of therapy (P0.001). Event-free survival (EFS) or overall survival (OS) did not differ between patients with or without ETV6-RUNX1 in Total XIIIA or XIIIB. By contrast, in Total XV, patients with ETV6-RUNX1 had significantly better EFS (P0.04; 5-year estimate, 96.82.4% versus 88.32.5%) and OS (P0.04; 98.91.4% versus 93.71.8%) than those without ETV6-RUNX1. Within the ETV6-RUNX1 group, the only significant prognostic factor associated with higher OS was the treatment protocol Total XV (versus XIIIA or XIIIB) (P0.01). Thus, the MRD-guided treatment schema including intensive asparaginase and high-dose methotrexate in the Total XV study produced significantly better outcomes than previous regimens and demonstrated that nearly all children with ETV6-RUNX1 ALL can be cured.

Original languageEnglish (US)
Pages (from-to)265-270
Number of pages6
JournalLeukemia
Volume26
Issue number2
DOIs
StatePublished - Feb 1 2012

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Residual Neoplasm
Disease-Free Survival
Survival
Therapeutics
Asparaginase
Clinical Protocols
Methotrexate
Leukemia
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Bhojwani, D., Pei, D., Sandlund, J. T., Jeha, S., Ribeiro, R. C., Rubnitz, J. E., ... Pui, C. H. (2012). ETV6-RUNX1-positive childhood acute lymphoblastic leukemia: Improved outcome with contemporary therapy. Leukemia, 26(2), 265-270. https://doi.org/10.1038/leu.2011.227

ETV6-RUNX1-positive childhood acute lymphoblastic leukemia : Improved outcome with contemporary therapy. / Bhojwani, D.; Pei, D.; Sandlund, J. T.; Jeha, S.; Ribeiro, R. C.; Rubnitz, J. E.; Raimondi, S. C.; Shurtleff, S.; Onciu, M.; Cheng, C.; Coustan-Smith, E.; Bowman, W. P.; Howard, Scott; Metzger, M. L.; Inaba, H.; Leung, W.; Evans, W. E.; Campana, D.; Relling, M. V.; Pui, C. H.

In: Leukemia, Vol. 26, No. 2, 01.02.2012, p. 265-270.

Research output: Contribution to journalArticle

Bhojwani, D, Pei, D, Sandlund, JT, Jeha, S, Ribeiro, RC, Rubnitz, JE, Raimondi, SC, Shurtleff, S, Onciu, M, Cheng, C, Coustan-Smith, E, Bowman, WP, Howard, S, Metzger, ML, Inaba, H, Leung, W, Evans, WE, Campana, D, Relling, MV & Pui, CH 2012, 'ETV6-RUNX1-positive childhood acute lymphoblastic leukemia: Improved outcome with contemporary therapy', Leukemia, vol. 26, no. 2, pp. 265-270. https://doi.org/10.1038/leu.2011.227
Bhojwani D, Pei D, Sandlund JT, Jeha S, Ribeiro RC, Rubnitz JE et al. ETV6-RUNX1-positive childhood acute lymphoblastic leukemia: Improved outcome with contemporary therapy. Leukemia. 2012 Feb 1;26(2):265-270. https://doi.org/10.1038/leu.2011.227
Bhojwani, D. ; Pei, D. ; Sandlund, J. T. ; Jeha, S. ; Ribeiro, R. C. ; Rubnitz, J. E. ; Raimondi, S. C. ; Shurtleff, S. ; Onciu, M. ; Cheng, C. ; Coustan-Smith, E. ; Bowman, W. P. ; Howard, Scott ; Metzger, M. L. ; Inaba, H. ; Leung, W. ; Evans, W. E. ; Campana, D. ; Relling, M. V. ; Pui, C. H. / ETV6-RUNX1-positive childhood acute lymphoblastic leukemia : Improved outcome with contemporary therapy. In: Leukemia. 2012 ; Vol. 26, No. 2. pp. 265-270.
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abstract = "ETV6-RUNX1 fusion is the most common genetic aberration in childhood acute lymphoblastic leukemia (ALL). To evaluate whether outcomes for this drug-sensitive leukemia are improved by contemporary risk-directed therapy, we studied clinical features, response and adverse events of 168 children with newly diagnosed ETV6-RUNX1-positive ALL on St Jude Total Therapy studies XIIIA (N36), XIIIB (N38) and XV (N94). Results were compared with 494 ETV6-RUNX1-negative B-precursor ALL patients. ETV6-RUNX1 was associated with age 1-9 years, pre-treatment classification as low risk and lower levels of minimal residual disease (MRD) on day 19 of therapy (P0.001). Event-free survival (EFS) or overall survival (OS) did not differ between patients with or without ETV6-RUNX1 in Total XIIIA or XIIIB. By contrast, in Total XV, patients with ETV6-RUNX1 had significantly better EFS (P0.04; 5-year estimate, 96.82.4{\%} versus 88.32.5{\%}) and OS (P0.04; 98.91.4{\%} versus 93.71.8{\%}) than those without ETV6-RUNX1. Within the ETV6-RUNX1 group, the only significant prognostic factor associated with higher OS was the treatment protocol Total XV (versus XIIIA or XIIIB) (P0.01). Thus, the MRD-guided treatment schema including intensive asparaginase and high-dose methotrexate in the Total XV study produced significantly better outcomes than previous regimens and demonstrated that nearly all children with ETV6-RUNX1 ALL can be cured.",
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AU - Jeha, S.

AU - Ribeiro, R. C.

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