Successful management of extreme hypertriglyceridemia in a child with acute lymphoblastic leukemia by temporarily omitting dexamethasone while continuing asparaginase

To the Editor: A 12-year-old female with no family history of lipid disorders diagnosedwith acute lymphoblastic leukemia (ALL) was treated according to Dutch Childhood Oncology Group (DCOG) ALL-10 protocol [1]. Based on minimal residual disease analysis at day 33 and 79, shewas stratified to themedium risk group (MRG) (Fig. 1A). Before start of intensification phase (week 1), serum levels of lipids and amylase were normal. These parameters were measured prospectively during intensive pegylated E. coli asparaginase (Oncaspar) administration. Triglyceride and total cholesterol levels increased after the first dexamethasone course and Oncaspar infusion. The maximum values of triglyceride (3,218mg/dl, normal upper level: 142mg/dl) and total cholesterol (770mg/dl, normal upper level: 213mg/dl) were noticed at week 19 of the intensification phase. In an attempt to lower the lipid levels, the dexamethasone course of week 22 was omitted (Fig. 1B). Administration of Oncaspar was continued every 2weeks according to protocol. The lipid values decreased dramatically to 279mg/dl for triglyceride and 487mg/dl for total cholesterol, both measured 1 week after omitting dexamethasone. Within 1 week after restarting dexamethasone at week 25, the triglyceride level increased and total cholesterol level was slightly reduced, 1,559 and 391mg/dl, respectively. The dexamethasone course at week 28 was therefore not administered and consequently the levels of triglyceride and total cholesterol decreased to almost normal levels (triglyceride 151mg/dl and total cholesterol 220mg/dl, both measured at week 29). From week 34 until end of treatment, the dexamethasone courses were definitely discontinued because of toxicity, among others, severe mood alteration (depression). The last measurement of triglyceride and cholesterol levels at week 42 revealed normal levels. Our patient had normal amylase levels and no signs of pancreatitis during asparaginase therapy. We demonstrate that extreme hypertriglyceridemia can be managed by omitting dexamethasone courses while continuing asparaginase infusions, without other therapy. We preferred to omit dexamethasone and not asparaginase to assure complete asparagine depletion during the first 30 weeks of the intensification phase. Dexamethasone courses are given 3-weekly during 84weeks, hence omitting a few courses was assumed a less significant reduction of therapy. Although lipid abnormalities associated with asparaginase are transient, it may be important to monitor triglyceride levels to prevent possible (future) complications [2]. For instance, triglyceride levels above 1,000mg/dl are suggested to cause triglyceride-induced pancreatitis [3]. Some clinicians do not treat these lipid abnormalities whereas others advise temporary fasting or low fat diet [2,4,5], oral fibrates [6], and plasmapheresis [2]. In conclusion, not asparaginase itself, but the combination of corticosteroids and asparaginase is responsible for severe disturbed lipid metabolism. Temporarily omitting corticosteroids is a good and safe strategy to try to normalize lipid levels when asparaginase infusions are combined with corticosteroids. However, omitting corticosteroids should be balanced with the risk of leukemia recurrence and may therefore be riskful in case the treatment protocol does not include further use of corticosteroids. Also, it is unclear at present what the consequences of a transient hyperlipidemia are.