Relapse after therapy is a major challenge for children and young adults with T-lymphocytic leukaemia (T-ALL), a subset of leukaemia sometimes associated with a poor prognosis.

Previous research has indicated that patients with a specific protein signature of T-ALL, called the early thymic precursor (ETP) immunophenotype, have particularly poor outcomes.

To better understand how the presence of this immunophenotype among pediatric T-ALL patients influences their response to therapy, researchers enrolled 1,144 T-ALL patients in this Phase III trial, the largest ever conducted among patients with this leukaemia subtype.

Included in the trial were children with the ETP immunophenotype (11.3%), children with a nearly identical type of T-ALL known as “near-ETP” (17%), and children without the ETP immunophenotype (71.6%).

After administering the same standard initial regimen to all children enrolled in the study, investigators measured levels of “minimal residual disease” (MRD – i.e., disease that is still detectable by sensitive techniques, but not by the pathologists’ traditional light microscope) in each patient, placing children into groups at low-, intermediate-, and high-risk of relapse (low risk <0.1% MRD; intermediate risk <1% MRD; and high risk >1% MRD), and providing therapy tailored to patients’ risk group.

Intermediate- and high-risk patients received additional radiation therapy and had the opportunity to be randomised to receive additional chemotherapy with nelarabine.

When researchers evaluated overall responses of all T-ALL patients enrolled in the trial, they observed that children with the ETP subset and near-ETP immunophenotypic signatures of T-ALL had a higher incidence of residual disease after initial treatment and most commonly fit into the higher-risk groups.

While ETP and near-ETP patients were more likely to fail initial treatment than those without these genetic signatures, all patients appeared to benefit from the tailored treatment regimen and experienced improvements in overall survival (OS; 93% OS among ETP patients; 91.6% OS among near-ETP patients; and 92% OS among non-ETP patients).

“When we looked at the overall outcomes among children with and without this form of T-ALL, we noticed that the children with the more aggressive subtypes had the same outcomes as other children with T-ALL, despite having a higher incidence of residual disease early after therapy,” said lead study author Brent Wood, MD, PhD, of the University of Washington in Seattle.

“This study represents the first large trial to demonstrate that patients with ETP T-ALL may have an outcome similar to that of other patients with this disease.”

Watch the press conference for more.

Source: ASH