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

Abstract

BACKGROUND:

The prognosis of patients with relapses of ETV6/RUNX1-positive acute lymphoblastic leukemia remains to be evaluated, particularly with regards to the frequency of late relapses. We performed a long-term, follow-up retrospective study to address the outcome of patients with ETV6/RUNX1-positive leukemia relapses.

DESIGN AND METHODS:

Among the 713 children tested for ETV6/RUNX1 enrolled into the FRALLE 93 protocol, 43 ETV6/RUNX1-positive patients relapsed (19.4%). Most were initially stratified in the low or intermediate risk groups. The median follow-up after relapse was 54.2 months. All but three received second-line salvage therapy and 16 underwent allogeneic transplantation.

RESULTS:

ETV6/RUNX1 had a strong effect on overall survival after relapse (3-year survival= 64.7% for positive cases versus 46.5% for negative cases) (P=0.007). The 5-year cumulative incidence of relapse was 19.4% and testes were more frequently involved in ETV6/RUNX1-positive relapses (P=0.04). In 81.4% of cases the relapses were late, early combined or isolated extramedullary relapses. The 5-year survival rate of patients with ETV6-RUNX1-positive acute lymphoblastic leukemia relapses reached 80.8% when the relapse occurred after 36 months (versus 31.2% when the relapse occurred earlier). In univariate analysis, female gender was associated with a poor survival, whereas site of relapse, age at diagnosis, leukocytosis and consolidation strategy had no effect. In multivariate analysis, only the duration of first remission remained associated with outcome.

CONCLUSIONS:

We found an excellent outcome for patients with ETV6/RUNX1-positive leukemia relapses that occurred more than 36 months after diagnosis. The duration of first complete remission may, therefore, be a guide to define the treatment strategy for patients with relapsed ETV6/RUNX1- positive leukemia.

• Authors: Virginie Gandemer, Sylvie Chevret, Arnaud Petit, Christiane Vermylen, Thierry Leblanc, Gérard Michel, Claudine Schmitt, Odile Lejars, Pascale Schneider, François Demeocq, Brigitte Bader-Meunier, Françoise Bernaudin, Yves Perel, Marie-Françoise Auclerc, Jean-Michel Cayuela, Guy Leverger, André Baruchel, FRALLE Group
• Journal: Haematologica (Haematologica) Vol. 97 Issue 11 Pg. 1743-50 (Nov 2012) ISSN: 1592-8721 [Electronic] Italy
• PMID: 22580999 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracyclines
• Core Binding Factor Alpha 2 Subunit
• Oncogene Proteins, Fusion
• TEL-AML1 fusion protein
• Vincristine
• Asparaginase
• Cortisone

Topics

• Adolescent
• Adult
• Anthracyclines (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Asparaginase (administration & dosage)
• Child
• Child, Preschool
• Core Binding Factor Alpha 2 Subunit
• Cortisone (administration & dosage)
• Disease-Free Survival
• Female
• Follow-Up Studies
• Hematopoietic Stem Cell Transplantation
• Humans
• Male
• Oncogene Proteins, Fusion
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (mortality, therapy)
• Recurrence
• Retrospective Studies
• Risk Factors
• Survival Rate
• Transplantation, Homologous
• Vincristine (administration & dosage)