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

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 (N=36), XIIIB (N=38) and XV (N=94). Results were compared to 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.

Excellent prognosis of late relapses of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia: lessons from the FRALLE 93 protocol

“…More recent protocols based on intensified chemotherapy schemes, especially with intensive use of L-asparaginase, 28 report lower frequencies of relapse for ETV6/RUNX1-positive ALL but should be examined with longer follow-up. 3,5,13,29 We also highlight that boys were slightly over-represented in our series, an imbalance which has been rarely reported except by Seeger et al and, more recently, by the NOPHO group. 15,27 Moreover, we observed a specific increase of testicular relapses in ETV6/RUNX1-positive ALL without any increase of relapses in other extramedullary sites (mainly CNS).…”

Molecular Genetic Studies on 167 Pediatric ALL Patients from Different Areas of Pakistan Confirm a Low Frequency of the Favorable Prognosis Fusion Oncogene TEL-AML1 (t 12; 21) in Underdeveloped Countries of the Region

“…Significant use of the drug L-asparaginase can benefit the patients with TEL-AML1 acute lymphoid leukemia Iqbal, (2006) and nearly all TEL-AML positive pediatric patients can be cured using intensive treatment protocols containing intensive asparaginase and high-dose methotrexate (Pui et al, 2008;Bhojwani et al, 2013). Furthermore, it is clinically established that, as compared to other genetic abnormalities, TEL-AML1 positive pediatric ALL patients shows excellent prognosis and outcome to standard treatment protocols being used in different regions of the world for treatment of this disease (Bhojwani et al, 2013;Mangolini et al, 2013). Thus, determination of TEL-AML1 fusion oncogene status at diagnosis and its percentage among other genetic abnormalities in pediatric ALL patients in a given population can significantly affect the outcome of treatment and can have a significant bearing on disease management policies related to pediatric ALL in a geographic region.…”

Genetic heterogeneity of infant acute leukemias

“…не выявлено ни одного пациента младше 1 года среди445ETV6-RUNX1-позитивныхбольных [20,21]. Сдругойстороны,M.Emerencianoисоавт.обнаружи-ли4позитивныхслучаясреди103пациентовпервого годажизни [2].…”