T-cell acute lymphoblastic leukemia: Current approach and future directions

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a rare subtype of ALL which primarily affects older children and young adults, with a male bias. Clinically, T-ALL presents with hyperleukocytosis, mediastinal disease, and/or involvement of the central nervous system. T-ALL is a high-risk subgroup within pediatric cohorts whereas among adults, outcomes are similar or better than that of B-cell acute lymphoblastic leukemia (B-ALL). Most T-ALL patients have mutations in NOTCH or FBXW7 (a NOTCH regulator) which suggests a common pathway of disease pathogenesis. The presence of one of these mutations confers a favorable prognosis in the absence of mutations in RAS and PTEN. Early T-precursor (ETP)-ALL is a high-risk subgroup of T-ALL that is characterized by stem-cell-like features, absence of NOTCH pathway mutations, and resistance to chemotherapy. Patients with T-ALL should be treated with intensive, ideally asparaginase-based, chemotherapy regimens. Allogeneic transplant is considered for consolidation of some adults with high-risk disease, including those with ETP-ALL or poor response to therapy. Relapsed T-ALL can be treated with nelarabine, but outcomes are poor and new therapies are needed.