Outcome of T-cell Acute Lymphoblastic Leukemia/Lymphoma: Focus on Near-ETP Phenotype & Differential Impact of Nelarabine.

Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) is characterized by a distinct immunophenotype (CD1a-negative, CD8-negative, CD5-negative or weak-positive <75%, myeloid/stem-cell markers positive) and poor clinical outcomes. Near-ETP ALL is transcriptionally similar to ETP-ALL but CD5 expression level is not low enough to meet the criteria of ETP immunophenotype. Outcomes of near-ETP ALL are not well characterized. We reviewed 171 patients with newly-diagnosed T-ALL/LBL. Patients were categorized into three groups; ETP (N=27), near-ETP (N=24), and non-ETP ALL/LBL (N=120). ETP-ALL/LBL was associated with a significantly worse survival compared with non-ETP ALL/LBL: 5-year overall survival (OS) rates 32% versus 63% (p < 0.001). Outcome was similar between near-ETP and non-ETP ALL/LBL: 5-year OS rates 56% versus 63% (p = 0.543). Landmark analysis showed that allogeneic stem cell transplant (allo-SCT) in first remission was beneficial in ETP-ALL/LBL (5-year event-free survival rates 36% versus 18%, p = 0.030) but not in near-ETP or non-ETP ALL/LBL. Multivariate analysis selected the following as significant independent prognostic factors for OS: age ≥60 years (HR 3.11; p = 0.003); elevated WBC ≥100×109 /L (HR 2.60; p = 0.005); and ETP immunophenotype (HR 2.29; p = 0.010). A survival advantage with adding nelarabine to hyper-CVAD was observed in non-ETP ALL (5-year OS rates 83% versus 38% with hyper-CVAD plus neralabine versus hyper-CVAD, p = 0.003). In conclusion, outcome of ETP-ALL/LBL was poor and improved with allo-SCT; outcome of near-ETP ALL/LBL was similar to non-ETP ALL/LBL; the addition of nelarabine to hyper-CVAD improved the survival in non-ETP ALL only. This article is protected by copyright. All rights reserved.