Aggressive Natural Killer Cell Leukemia: A Brief Overview of Its Genomic Landscape, Histological Features, and Current Management

Aggressive natural killer-cell leukemia (ANKL) is a rare hematological malignancy characterized by the abnormal proliferation of natural killer (NK) cells. There are currently no therapies approved by the US Food and Drug Administration (FDA) for the treatment of ANKL, but advancements in genomics are assisting in the unraveling of this rare malignancy. We selected 37 articles that contained information on genomics, immunohistochemistry, and/or current clinical trials relating to the treatment and survival of ANKL. Current therapeutic strategies have been subdivided into (1) concurrent chemoradiation, (2) sequential chemoradiation, and (3) sandwich chemoradiation. These methods have been developed to reduce toxicity while still producing a pathologic response. Concurrent chemoradiation with VIDL (etoposide, ifosfamide, dexamethasone, and L-asparaginase) produced an excellent clinical response, while sequential chemoradiation with SMILE (steroid dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) showed an adequate response, but with severe hematologic toxicity. The efficacy of L-asparaginase in chemotherapeutic regimens and its association with NK-cell apoptosis have led to its inclusion in all standard regimens. Future studies are focusing on the addition of a programmed death-ligand 1 (PD-L1) inhibitor and hematopoietic stem cell transplant (HSCT).