Gugliotta L, Mazzucconi M G, Leone G, Mattioli-Belmonte M, Defazio D, Annino L, Tura S, Mandelli F
Istituto di Ematologia, L. e A. Seràgnoli, Policlinico S. Orsola, Bologna, Italy.
Eur J Haematol. 1992 Aug;49(2):63-6. doi: 10.1111/j.1600-0609.1992.tb00032.x.
The incidence of thrombotic complications chronologically related to L-asparaginase administration is retrospectively analyzed in 238 adult ALL patients treated according to the GIMEMA protocol ALL 0288. The patients (126 males and 112 females, aged 12-68 years, median 29) received E. coli L-asparaginase (L-ase) in the induction phase at a dosage of 6000 U/m2/day x 7 d starting on d 15, as well as vincristine, prednisone, daunorubicin and cyclophosphamide, the last-named by random 1:1. Ten patients (4.2%) developed thrombotic complications 5-15 d (median 11 d) after the start of L-ase treatment. The thrombotic events, which were lethal in 5 patients, involved the cerebral sinus (5 cases), the cerebral arteria (2 cases), the portal vein (1 case), the pulmonary district (1 case), and a deep vein in the lower extremity (1 case). The occurrence of these complications was not related to the general thrombotic risk factors, nor to the main clinical and laboratory data registered at diagnosis and immediately before the start of L-asparaginase treatment. The present study documents for the first time in a sufficiently large series of adult ALL patients that the incidence and the severity of thrombotic events related to L-ase administration are relevant and need further consideration.
回顾性分析了238例按照GIMEMA方案ALL 0288治疗的成年急性淋巴细胞白血病（ALL）患者中，与L-天冬酰胺酶给药按时间顺序相关的血栓形成并发症的发生率。这些患者（126例男性和112例女性，年龄12 - 68岁，中位数29岁）在诱导期从第15天开始接受大肠杆菌L-天冬酰胺酶（L-ase）治疗，剂量为6000 U/m²/天，共7天，同时还接受长春新碱、泼尼松、柔红霉素和环磷酰胺，最后一种药物随机按1:1使用。10例患者（4.2%）在L-ase治疗开始后5 - 15天（中位数11天）出现血栓形成并发症。这些血栓形成事件导致5例患者死亡，累及脑窦（5例）、脑动脉（2例）、门静脉（1例）、肺区（1例）和下肢深静脉（1例）。这些并发症的发生与一般血栓形成危险因素无关，也与诊断时以及L-天冬酰胺酶治疗开始前即刻记录的主要临床和实验室数据无关。本研究首次在足够大样本量的成年ALL患者系列中证明，与L-ase给药相关的血栓形成事件的发生率和严重程度值得关注，需要进一步研究。
