Persson Lisa, Harila-Saari Arja, Hed Myrberg Ida, Heyman Mats, Nilsson Anna, Ranta Susanna
Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Pediatr Blood Cancer. 2017 Oct;64(10). doi: 10.1002/pbc.26559. Epub 2017 Apr 25.
Asparaginase (ASP) is a cornerstone in the treatment of acute lymphoblastic leukemia (ALL). It is also known for its ability to cause side effects, such as allergy and pancreatitis, as well as lipid and coagulation disturbances. The most important laboratory abnormalities are hypertriglyceridemia (HTG) and low antithrombin (AT). HTG is usually considered to be transient and benign in children with ALL, whereas low AT activity predisposes to thrombosis. Studies on the incidence and significance of HTG in children with ALL are scarce, and their findings have not always been congruent. We investigated the incidence and significance of ASP-related HTG, defined as triglyceride values more than five times the upper normal limit, in children with ALL.
We analyzed the laboratory and clinical data of children diagnosed with ALL at the Karolinska Hospital, Stockholm, Sweden, from July 2008 to December 2014. Triglyceride and AT values were measured before each injection of pegylated ASP.
The study group comprised of 92 patients, aged 1-17.9 years at diagnosis (median 4.8 years), almost half (42/92, 46%) of whom had HTG. A significant negative correlation between triglyceride and AT values was observed in those aged over 10 years (P = 0.0002). No significant correlation was found between HTG and thrombosis, osteonecrosis, or pancreatitis.
Although common, ASP-associated HTG was not associated with other ASP-related toxicities. HTG correlated with decreased AT activity in older children, which may explain previous association between HTG and thrombosis. Larger studies are of interest with regard to establishing guidelines for HGT management.
天冬酰胺酶(ASP)是治疗急性淋巴细胞白血病(ALL)的基石。它也因其引发副作用的能力而闻名,如过敏、胰腺炎以及脂质和凝血紊乱。最重要的实验室异常是高甘油三酯血症(HTG)和低抗凝血酶(AT)。HTG在ALL患儿中通常被认为是短暂且良性的,而低AT活性易引发血栓形成。关于ALL患儿中HTG的发生率及意义的研究较少,且研究结果并不总是一致。我们调查了ALL患儿中与ASP相关的HTG(定义为甘油三酯值超过正常上限五倍)的发生率及意义。
我们分析了2008年7月至2014年12月在瑞典斯德哥尔摩卡罗林斯卡医院被诊断为ALL的患儿的实验室和临床数据。在每次注射聚乙二醇化ASP之前测量甘油三酯和AT值。
研究组包括92例患者,诊断时年龄为1 - 17.9岁(中位数4.8岁),其中近一半(42/92,46%)患有HTG。在10岁以上的患儿中观察到甘油三酯和AT值之间存在显著的负相关(P = 0.0002)。未发现HTG与血栓形成、骨坏死或胰腺炎之间存在显著相关性。
尽管常见,但与ASP相关的HTG与其他ASP相关毒性无关。HTG与年龄较大患儿的AT活性降低相关,这可能解释了之前HTG与血栓形成之间的关联。关于制定HGT管理指南,有必要进行更大规模的研究。