Biology and Treatment Paradigms in T Cell Acute Lymphoblastic Leukemia in Older Adolescents and Adults

T cell acute lymphoblastic leukemia (T-ALL) occurs in approximately 25-30% of adult ALL diagnoses. Historically, B cell ALL (B-ALL) and T-ALL have been treated in the same fashion despite differences in the biology of disease. Outcomes in the adolescent/young adult (AYA) population have improved significantly with the utilization of pediatric-based regimens. In addition, there may now be a role for the addition of nelarabine to frontline treatment in the AYA population. In older adults, choices in which regimen to pursue should account for the potential toxicities associated with pediatric-based regimens. Measurable residual disease (MRD) has taken on increasing prognostic value in T-ALL and may help to identify which patients should receive an allogeneic stem cell transplant. T cell lymphoblastic lymphoma (T-LBL) has traditionally been treated similarly to T-ALL, but additional management questions must be considered. Mediastinal irradiation does not seem to clearly improve outcomes, and there is considerable heterogeneity in the central nervous system (CNS) prophylaxis strategy used in prospective trials. CNS prophylaxis in AYA patients with T-ALL, on the other hand, can be safely achieved with intrathecal chemotherapy alone. Prospective data regarding CNS prophylaxis strategies in older adults are currently not available. Nelarabine-based regimens currently remain the standard in relapsed/refractory T-ALL; however, novel therapies targeting molecular aberrations in T-ALL are actively being investigated.