门冬酰胺酶治疗血液肿瘤致高甘油三酯血症的临床研究

Asparaginase for therapy of transient hypertriglyceridemia caused by hematologic neoplasms

为了研究门冬酰胺酶（ASP）治疗血液肿瘤时致高甘油三酯血症（HTG）的发生率、临床特点和治疗，以引起临床对该副反应的重视，对24例儿童和成人急性淋巴细胞白血病（ALL）、淋巴母细胞淋巴瘤和NK／T细胞淋巴瘤患者接受了含ASP的联合化疗方案治疗，测定治疗前后的血胆固醇和甘油三酯（TG）水平，确定血脂异常的发生率和特点。24例患者共接受36个周期含ASP的联合方案化疗，2例次出现HTG，发生率为5．6％。2例均为成人ALL，均在初次缓解后4和5个月，再次使用ASP进行巩固治疗时出现HTG，峰值TG分别为32．57和15．77mmol／L。1例同时伴有下肢剧烈疼痛。停用ASP并加用胰岛素静脉滴入治疗，9～11d后血脂均恢复正常。初步研究结果提示，接受ASP治疗的血液肿瘤患者有发生HTG的危险，尽管此种HTG在停药多后多可恢复，但可继发胰腺炎、高黏滞综合征或血栓。因而ASP治疗时应常规监测血TG水平。

The objective of this study was to investigate the incidence, clinical characteristics and treatment of asparaginase（ASP）-associated hypertriglyceridemia in adult and children with hematologic neoplasms, and draw attention to this side effects. Twenty-four newly diagnosed children and adult with acute lymphoblastic leukemia（ALL）, lymphoblastie lymphoma and NK/T lymphoma were retrospectively evaluated for lipid abnormalities. They were treated with a regimen containing ASP between 2006 and 2010. Total cholesterol and triglycerides （TG） levels were measured in all patients before and after use of ASP. All 24 patients received 36 cycles chemotherapy including ASP. ASP associated-hypertriglyceridemia occured in 2 cycles of 2 adult patients with ALL（5.6%）. Transient hypertriglyceridemia （32.57 mmol/L and 15. 77 mmol/L） was observed following administration of ASP as intensification treatment after 4 and 5 months of complete remission. One patient reported pain in both lower extremities associated with hypertriglyceridemia. Cessation of ASP use and lipolytic therapy with insulin resulted in a prompt and continuous decrease in serum lipid levels. The elevated TG levels were normalized within 9--11 days. In conclusion, The patients suffering from hematologic neoplasms treated with ASP are at risk of developing severe lipid abnormalities. Although hypertriglyceridemia due to ASP is reversible after drug discontinuation,it is associated with severe complications such as pancreatitis and hyperviscosity syndrome. Routine laboratory monitoring should therefore include triglyceride and cholesterol levels in all patients receiving ASP.