Biology and treatment of childhood T-lineage acute lymphoblastic leukemia.

ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) is the most prevalent type of cancer, as well as the most common form of leukemia in children.1 This lymphoid malignancy, manifested by the proliferation of lymphopoietic blast cells, represents a heterogeneous group of diseases that vary with respect to morphological, cytogenetic, and immunologic features of the transformed cells. Technical improvements in immunofluorescence staining and flow cytometry together with the availability of numerous monoclonal antibodies (MoAbs) that recognize lineage-associated membrane molecules have illuminated the immunophenotypic heterogeneity in ALL. We now know that leukemia cells from patients with ALL may express various combinations of surface antigens that are found normally on lymphocyte precursors at discrete stages of maturation.2,3 Thus, the malignant clones in patients with ALL are thought to originate from normal lymphoid progenitor cells arrested at early stages of Bor T-lymphocyte ontogeny. Although cells from the majority (<85%) of pediatric patients express B-lineage–associated antigens, those from approximately 15% of patients express the T-lineage–associated antigens CD1, CD2, CD3, CD4, CD5, CD7, or CD8.4-6 T-lineage ALL in children is associated with numerous unfavorable presenting features, thus it is not surprising that children with T-lineage ALL frequently have been reported to have a worse prognosis than children with B-lineage ALL.4,5,7-10 However, a number of encouraging reports from recent clinical studies using contemporary risk-adjusted multiagent chemotherapy programs have documented remarkably improved outcomes for patients with T-lineage ALL.6,10-14 Moreover, advanced preclinical studies have triggered much optimism that new agent discovery programs may lead to further improvements in outcome in the near future. In this review, we discuss current concepts regarding the etiology, biological characteristics, clinical features, and treatment of pediatric T-lineage ALL.