Advances in the treatment and prognosis of aggressive NK-cell leukemia: results from the ANKL22 study.

Aggressive NK-cell leukemia (ANKL) is a rare NK-cell leukemia characterized by, an aggressive clinical course, and frequent Epstein-Barr virus association. We retrospectively collected 126 ANKL patients diagnosed between 2000 and 2021 from 71 institutes; 108 were evaluable for analysis to characterize the recent advances. The median age was 49 years (range: 17-90), and 63 patients were male. The median percentage of leukemic cells in the bone marrow and peripheral blood was 19.7% and 10.0%, respectively. The first-line regimens included SMILE (n = 38, 42%), CHOP(-like) (n = 26, 29%), DeVIC (n = 15, 17%), and other L-asparaginase-containing regimens (n = 8, 9%), with the overall response rates of 66%, 31%, 33%, and 50%, respectively. Median overall survival (OS) was 5.5 months, with a 2-year OS of 18.7%. Patients treated with SMILE had significantly better OS than others (2-year OS 30.1% vs. 7.0%; P < 0.001). Prognosis further improved with allogeneic hematopoietic stem cell transplantation (HSCT) (2-year OS 37.2% vs 3.5%; P < 0.001). Multivariate analysis confirmed treatment with SMILE [hazard ratio (HR) 0.53, 95% confidential interval (CI) 0.31-0.88] and allogeneic HSCT (HR 0.33, 95% CI 0.18-0.61) as independent favorable factors. In conclusion, SMILE chemotherapy followed by allogeneic HSCT may improve outcomes in ANKL.