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ETV6-RUNX1-positive childhood acute lymphoblastic leukemia: improved outcome with contemporary therapy

2011; Springer Nature; Volume: 26; Issue: 2 Linguagem: Inglês

10.1038/leu.2011.227

1476-5551

Deepa Bhojwani, D. Pei, J T Sandlund, Sima Jeha, R C Ribeiro, Jeffrey E. Rubnitz, S C Raimondi, Sheila Shurtleff, Mihaela Onciu, Christopher H.K. Cheng, Elaine Coustan‐Smith, W. Paul Bowman, Scott C. Howard, Monika L. Metzger, Hiroto Inaba, Wing Leung, William E. Evans, Dario Campana, Mary V. Relling, C-H Pui,

Acute Myeloid Leukemia Research

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 (N=36), XIIIB (N=38) and XV (N=94). 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 (P<0.001). 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 (P=0.04; 5-year estimate, 96.8±2.4% versus 88.3±2.5%) and OS (P=0.04; 98.9±1.4% versus 93.7±1.8%) 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) (P=0.01). 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.