Aggressive natural killer cell leukemia: therapeutic potential of L-asparaginase and allogeneic hematopoietic stem cell transplantation

Abstract

We conducted a retrospective Japan-Korea multicenter study to better elucidate the clinicopathologic features and therapeutic modalities for aggressive natural killer cell leukemia (ANKL). A total of 34 patients were analyzed. The median age of the patients was 40 years. Among the patients in the study, four had a history of Epstein-Barr virus-related disorders. Three types of ANKL cells were categorized according to their morphological features. Leukemic cells were below 20% in both peripheral blood and bone marrow of 11 patients. The clinical characteristics and prognoses of these 11 patients did not differ significantly from those of the others. As an initial therapy, l-asparaginase chemotherapy resulted in a better response. A total of six patients received allogeneic hematopoietic stem cell transplantation (HSCT) and two received autologous HSCT, with all in non-complete remission (CR). After HSCT, four with allogeneic and one with autologous HSCT reached CR. Median survival of all patients was 51 days. Median survival for the patients with and without HSCT were 266 and 36 days, respectively. A total of two patients with allogeneic HSCT were alive and in CR. All patients without HSCT died of ANKL. The use of L-asparaginase was indicated as a factor for longer survival (HR 0.33, 95% confidence interval; 0.13-0.83, P = 0.02). Early diagnosis of ANKL, l-asparaginase-based chemotherapy and allogeneic HSCT might lead to improved patient outcomes.

Figure 1

Morphology of aggressive NK‐cell leukemia cells. Three types of leukemic cells were classified. Type I (a) are large granular lymphocytes. Type III (c) are pleomorphic and atypical cells with prominent nucleoli. Type II (b) shows intermediate morphology between types I and III.

Figure 2

Age and sex distribution of the patients. Age range is indicated on the abscissa; the number of the patients is shown on the ordinate.

Figure 3

Survival curve of all patients with aggressive natural killer cell leukemia.

Figure 4

Initial chemotherapy for aggressive natural killer cell leukemia. (a) Survival curve with (dotted line) or without (solid line) anthracycline‐based regimens. (b) Survival curve with (dotted line) or without (solid line) l‐asparaginase‐combined chemotherapy.

Figure 5

Hematopoietic stem cell transplantation (HSCT) for aggressive natural killer cell leukemia. Survival curve of the patients without HSCT (solid line, N = 26) and the patients who received HSCT (dotted line, N = 8).