The mature T-cell and natural killer (NK) cell lymphomas represent 10 to 15 percent of the non-Hodgkin lymphomas by incidence and comprise 23 clinicopathologic entities in the most recent classification. They include cutaneous T-cell lymphomas, discussed in Chap. 14, and systemic T-cell lymphomas, which are discussed here. The systemic T-cell lymphomas have highly variable courses and are typically aggressive and frequently less 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 percent and 19 percent 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. Treatment strategies are generally based upon 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, and prednisone (CHOP) based, although long-term outcomes are often unsatisfactory. Therefore, ongoing clinical trials are aimed at improving upon 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 remission durations. Recently, targeted agents specific for particular T-cell and NK cell lymphomas, such as brentuximab vedotin for ALCL and crizotinib for anaplastic lymphoma kinase (ALK)–positive ALCL, are now allowing the investigation of more individualized therapy for these entities. Furthermore, for a considerable number of the T-cell and NK cell lymphoma entities, including ENKTL and ATL, CHOP-based therapy is 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 may help answer some of these questions. In addition, it is hoped that ongoing clinical trials evaluating disease-specific treatment approaches and the use of novel and often targeted agents will 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 percent of non-Hodgkin lymphomas and are made up of 23 heterogeneous diseases (Table 15–1).1,1a 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 percent of cases. This overview primarily pertains to these most common subtypes of PTCL, and more detailed discussion of other subsets of PTCL follows this discussion.
TABLE 15–1.2016 WHO Classification of Mature T-Cell and Natural Killer Cell Neoplasms (Excluding Primary Cutaneous Lymphomas)