Natural killer/T-cell lymphomas in pediatric and adolescent patients

Natural killer/T-cell (NK/T-cell) lymphomas are rare in children and adolescents and consist predominantly of nasal-type extranodal NK/T-cell lymphomas. More than half of pediatric/adoles-cent patients with NK/T-cell lymphomas present with localized nasal/sinus involvement, but the disease may involve many organs. NK/T-cell lymphoma cells are cytotoxic and associated with necrosis and angioinvasion; they express CD56, CD2, cytoplasmic CD3 epsilon, and to a variable degree CD30. The cells contain Epstein-Barr virus (EBV)–encoded RNA. Loss of chromosome 6q is frequent, and multiple other genetic changes may occur. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) and other pathways are activated in NK/T-cell lymphoma. Adults with stage I/II disease receive radiation with or without chemotherapy, whereas adults with advanced disease receive multiagent chemotherapy, including asparaginase and drugs not affected by P-glycoprotein–mediated resistance. Outcomes data for pediatric patients come from retrospective reviews and retrospective case series. The overall survival of pediatric patients is 77% for those with stage I/II disease and 36% to 59% for those with advanced disease. Bone marrow transplant (BMT) is used in children, but with little evidence regarding the indications and rationale for type of transplant. BMT achieves better outcomes for adult patients in remission, but with high levels of morbidity and mortality. Improved understanding of the biology of this disease will allow the development of targeted approaches, including JAK/STAT inhibitors, checkpoint inhibitors, anti-CD30 agents, epigenetic modifiers, and reduced-intensity conditioning for BMT, to improve outcomes in pediatric patients.