Angioimmunoblastic T-Cell Lymphoma: Clinical Aspects and Recent Advances in Biology and Therapy

Angioimmunoblastic T-cell lymphoma (AITL) comprehends 20% of the peripheral T-cell lymphomas (PTCL). Although rare, its clinical features may overlap with many other inflammatory, infectious or neoplastic disorders. Therefore, that patients are often diagnosed with advanced stage disease, which contributes for the disease´s dismal prognosis. The clinical presentation of AITL is frequently an assemblage of symptoms including generalized and painful lymphadenopathy, multiple cutaneous alterations, hypergammaglobulinemia, fever, loss of weight and significant autoimmune phenomena. Recent advances in AITL biology have implicated a cell with T-follicular helper phenotype as the origin of the disorder. This rare type of T lymphocyte has a peculiar capacity of interact with microenviroment, which results in an important production of cytokines, explaining the clinical findings of this type of lymphoma. In addition to its pathologic features, AITL can be distinguished from other T-cell lymphomas based on gene expression arrangement, suggesting that AITL has a unique biology. Moreover, somatic mutations in the epigenetic regulators DNMT3A, TET2, IDH2, and, especially, in the multifunctional RHOA GTPase gene, have emerged as very consistent genetic abnormalities in AITL. Considering its low incidence, the development of clinical trials in AITL is a challenging matter. Furthermore, the majority of data available originates from studies that contain other subtypes of PTCL, making prognosis analysis and treatment decision a tough work. In this review, we discuss the biological and clinical aspects of AITL and the alternatives for frontline treatment and the management of relapsed disease.