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

Abstract

The online version of this article has a Supplementary Appendix. BackgroundThe 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 MethodsAmong 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. ResultsETV6/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. ConclusionsWe 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.

Treatment of Pediatric Acute Lymphoblastic Leukemia

“…For example, those with relapsed disease who demonstrate ETV6-RUNX1 mutations have a relatively favorable prognosis, with an event-free survival of more than 80% if initial CR1 was at least 36 months. 42 Conversely, blasts demonstrating TP53 mutations show a particularly poor prognosis. 43 …”

The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system

“…In order to mimic pre-BCR and pre-Tcell receptor (TCR) activation as controls, 697 cells were Figure 3B). Upon stimulation with CCL19, 697 cells displayed an increase in p-ERK1/2 as compared to unstimulated cells, but to a lesser extent than in response to anti-IgM F(ab) 2 ( Figure 3B, left). Similarly, JURKAT cells showed an increase in p-ERK after 5 min of CCL19 stimulation ( Figure 3B, right), which declined after 30 min (data not shown).…”

“…Cell viability was measured using trypan blue. CD19, CD3ε, hCD45, mCD45, CCR7, CXCR4 and ZAP70 antibodies were purchased from eBioscience or Santa Cruz Biotechnology, p-ERK/ERK and b-tubulin antibodies from Cell Signaling Technology, anti-Immunoglobulin M (IgM) F(ab) 2 from SouthernBiotech, and U0126 from LC Laboratories. …”

Effects of p38α/β inhibition on acute lymphoblastic leukemia proliferation and survival in vivo

“…2 Relapses in patients with favorable cytogenetics such as TEL-AML1 are particularly devastating to patients and physicians as they often occur long after termination of therapy and are unpredictable. 3 Unlike in other hematological malignancies, targeted approaches aiming to increase therapy specificity are limited. These findings emphasize the need for new diagnostic and therapeutic strategies further improving long-term outcomes.…”