Outcome of T‐cell acute lymphoblastic leukemia/lymphoma: Focus on near‐ETP phenotype and differential impact of nelarabine

Abstract

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\u2009<\u2009.001). Outcome was similar between near‐ETP and non‐ETP ALL/LBL: 5‐year OS rates 56% versus 63% (p = .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 = .030) but not in near‐ETP or non‐ETP ALL/LBL. Multivariate analysis selected the following as significant independent prognostic factors for OS: age\u2009≥\u200960\u2009years (HR 3.11; p = .003); elevated WBC ≥100\u2009×\u2009109/L (HR 2.60; p = .005); and ETP immunophenotype (HR 2.29; p = .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 = .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.