Central Nervous System Progression/Relapse in Mature T- and NK-Cell Lymphomas

Simple Summary Mature T- and NK-cell neoplasms are a heterogeneous group of disease entities that comprise about 15% of non-Hodgkin lymphomas. These subtypes are often aggressive, especially in the relapsed/refractory setting. In particular, central nervous system progression/relapse is a rare but devastating outcome for these patients. Moreover, relative infrequency and heterogeneity of tumor biology have precluded the ability to establish standards of care for prophylaxis and treatment of patients with secondary central nervous system involvement. This review describes the epidemiology and risk factors of central nervous system progression/relapse in patients with mature T- and NK-cell lymphomas and discusses the role of prophylaxis and therapy. Non-Hodgkin lymphomas (NHL) are cancers of mature B-, T-, and NK-cells which display marked biological heterogeneity between different subtypes. Mature T- and NK-cell neoplasms are an often-aggressive subgroup of NHL and make up approximately 15% of all NHL. Long-term follow up studies have demonstrated that patients with relapsed/refractory disease have dismal outcomes; in particular, secondary central nervous system (CNS) involvement is associated with higher mortality, though it remains controversial whether this independently confers worse outcomes or if it simply reflects more aggressive systemic disease. Possible risk factors predictive of CNS involvement, such as an elevated lactate dehydrogenase and more than two sites of extranodal involvement, may suggest the latter, though several studies have suggested that discrete sites of anatomic involvement or tumor histology may be independent risk factors as well. Ultimately, small retrospective case series form the basis of our understanding of this rare but devastating event but have not yet demonstrated a consistent benefit of CNS-directed prophylaxis in preventing this outcome. Nonetheless, ongoing efforts are working to establish the epidemiology of CNS progression/relapse in mature T- and NK-cell lymphomas with the goal of identifying clinicopathologic risk factors, which may potentially help discern which patients may benefit from CNS-directed prophylactic therapy or more aggressive systemic therapy.