Abstract
L-Asparaginase (ASP)-induced thrombosis (AIT) is a serious complication related to the treatment of acute lymphoblastic leukemia (ALL) and lymphoma. However, its epidemiology and management remain to be determined in the pediatric population in Japan. Here, to investigate the incidence and characteristics of AIT, and to survey the coagulation tests performed and anticoagulant prophylaxis during ASP-containing induction therapy for childhood ALL and lymphoma in Japan, a retrospective survey of 96 JACLS treatment centers was conducted. Forty-seven (49%) of the centers responded. Among 1,586 patients treated with ASP from 2002 to 2011, eight (0.50%) were found to have AIT. Of these eight patients, seven experienced AIT during the induction phase, and in six of them, AIT was located in the central nervous system. A steroid was concurrently used in all the patients with AIT. Four of the eight patients had fever and two had bacteremia. At the onset of AIT, the median antithrombin (AT) activity was 71% (range, 53–90%), the fibrinogen concentration was 93 mg/dL (29.8–260 mg/dL), and the D-dimer concentration was 2.2 μg/mL (1.0–4.6 μg/mL). One patient died of AIT and another suffered from AIT-related sequelae. Among the 45 centers that provided information, 40 (89%) measured AT activity twice or three times a week, 43 (96%) prophylactically administered an AT concentrate, and 21 (47%) routinely transfused with fresh frozen plasma during the induction therapy with ASP. AIT occurred despite the prophylaxis with the AT concentrate. No test could predict the onset of AIT accurately. Novel markers and a preventive strategy for AIT need to be established.
