The mature T-cell and natural killer (NK)-cell lymphomas represent 10% to 15% of the non-Hodgkin lymphomas by incidence and comprise 28 clinicopathologic entities in the most recent classification. They include cutaneous T-cell lymphomas, discussed in Chap. 102, and systemic T-cells lymphomas, which are discussed here. The systemic T-cell lymphomas have highly variable courses and are typically aggressive and frequently less reliably responsive to conventional chemotherapy than their B-cell counterparts. The most common systemic T-cell and NK-cell lymphomas worldwide include peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL), representing 26% and 19% of systemic T-cell and NK-cell lymphomas, respectively. There is considerable geographic variation in the incidence of certain entities, such as adult T-cell leukemia/lymphoma (ATL) and extranodal NK-/T-cell lymphoma (ENKTL). In view of the rarity of systemic T-cell and NK-cell disorders, large randomized trials are lacking to guide therapies and treatment strategies for many subsets of T-cell lymphomas. Management must then be based on the best data available, which includes prospective phase II studies and retrospective analyses. The most frequently used regimens for the more common entities, PTCL-NOS, AITL, and anaplastic large cell lymphoma (ALCL) are cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) based, although long-term outcomes are often unsatisfactory. A randomized, phase III study has recently shown that patients with expression of CD30 benefit from the addition of brentuximab vedotin (BV) to cyclophosphamide, doxorubicin, and prednisone (CHP). Other ongoing clinical trials are aimed at improving on CHOP by adding novel agents or using alternate regimens. Although controversial, patients are often considered for consolidation with autologous stem cell transplant in first remission to improve rates of durable remissions. Targeted agents specific for particular T-cell and NK-cell lymphomas, such as BV for ALCL and crizotinib for anaplastic lymphoma kinase (ALK)-positive ALCL, highlight a newer paradigm for investigation of more individualized therapies targeting specific subtypes of PTCL. Furthermore, for a considerable number of the T-cell and NK-cell lymphoma entities, including ENKTL and ATL, CHOP-based therapy is largely ineffective, and treatment strategies are disease specific. There is still much to learn about the biology and potential drug targets for these diseases, and ongoing studies using gene expression profiling and genomics are beginning to answer some of these questions. In addition, ongoing clinical trials evaluating disease-specific treatment approaches and using novel agents in a targeted fashion will hopefully lead to improved outcomes for patients with these diseases.
OVERVIEW OF MATURE T-CELL LYMPHOMAS
The peripheral T-cell lymphomas (PTCLs) represent approximately 10% to 15% of non-Hodgkin lymphomas (NHLs) and are made up of 28 heterogeneous diseases (Table 103–1).1 The most common entities, peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), and ALK-negative ALCL, account for approximately 60% to 65% of cases by incidence in North America and Europe. This overview primarily pertains to these most common subtypes of PTCL; more detailed discussion ...