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

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.