T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy that has historically been associated with a very poor prognosis. Nevertheless, despite a lack of incorporation of novel agents, the development of intensified T-ALL focused protocols has resulted in significant improvements in outcome in children. Through the use of several representative cases, we highlight the key changes that have driven these advances including asparaginase intensification, the use of induction dexamethasone, and the safe omission of cranial radiotherapy (CRT). We discuss the results of recent trials to explore key topics including the implementation of risk stratification with minimal residual disease (MRD) measurement and how to treat high-risk subtypes such as early T cell precursor (ETP) ALL. In particular, we address current discrepancies in treatment between different cooperative groups, including the use of nelarabine, and provide rationales for current treatment protocols for both T-ALL and T-lymphoblastic Lymphoma (T-LL).

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