Novel Targeted Therapeutics for Peripheral T-Cell Lymphoma

Abstract

The peripheral T-cell lymphomas (PTCL) are a group of aggressive mature T-cell and natural killer cell (NK) neoplasm’s that present with great morphological and molecular heterogeneity (Anderson et al. 1998). They are relatively rare diseases, constituting <15 % of all NHL’s (Groves et al. 2000). The present 2008 WHO classification recognizes over 20 sub-types of mature T-cell and NK-cell malignancies (WHO 2008). These sub-types are listed in Table 1 along with the annual incidence rates and 3 year survival rates as reported in the SEER database (Seer Cancer Statistic 1975). The most common histologies include: PTCL, not otherwise specified (PTCL-NOS); anaplastic large cell lymphoma (ALCL) and angioimmunoblastic T-cell lymphoma (AITL). Similar to the B-cell neoplasm’s, the T-cell lymphomas can be broadly classified as aggressive or indolent malignancies. The most aggressive histologies include PTCL-NOS, hepatosplenic T-cell lymphoma, the gamma/delta T-cell malignancies and extranodal NK/T-cell nasal type lymphoma. PTCL-NOS is often viewed as a “wastebasket” category for those diseases that do not fit cleanly into the other sub-types. Most cases of PTCL lack distinct genetic or biological alterations and prognostic models have largely relied on clinical features or simple biological factors such as proliferation. Despite a relatively poor understanding of the molecular pathogenesis of these diseases, significant progress has been made in the understanding of many PTCL entities. For example, ALK positive anaplastic large cell lymphoma (ALCL) is considered a distinct disease entity which is distinguished from the provisional entity of ALK negative ALCL, due to the distinct molecular pathogenesis, relatively younger age group in which it presents and better prognosis. Based on the recent publications from the ‘The International T-cell Lymphoma Project’, an international effort of over 22 centers worldwide which collected data from over 1,314 cases of T-cell and NK -cell lymphoma, we now recognize that PTCL-NOS is a distinct entity from ALK negative ALCL as the former is associated with a markedly inferior prognosis (Vose et al. 2008) Table 2.