Abstract CT409: Dexamethasone (dex) and asparaginase increase triglycerides during acute lymphoblastic leukemia (ALL) therapy in children
Authors: Ramsey Laura B. , Robinson Katherine M. , Kawedia Jitesh D. , Yang Wenjian , Liu Chengcheng , Panetta John C. , Jeha Sima , Bhojwani Deepa , Metzger Monika L. , Cheng Cheng , Evans William E. , Pui Ching-Hon , Relling Mary V. 
Published: May 2015

Although dyslipidemia has been reported during ALL therapy, there have been few systematic studies, and no prior study with dex pharmacokinetics (PK) or asparaginase biomarkers. We studied serum high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, and cholesterol in 313 pediatric ALL patients enrolled on St. Jude Total XV at baseline (day 15 consolidation), and weeks (wks) 7, 8 and 12 of continuation therapy. Patients on the standard/high risk (SHR) arm (n=163) were exposed to more asparaginase (wks 1-12) than those on the low risk (LR) arm (n=150, wks 7-9) as reflected by lower serum albumin at wks 7, 8, and 12 (p &lt;10-6, all time points). Dex was given during wks 1, 4, 7, and 9. Dex PK was assessed at the start and end of wk 7.

LDL decreased after asparaginase (wk 8 in the LR and wk 7 in the SHR arm). HDL decreased from wk 7 to 8, after one wk of dex and asparaginase. Cholesterol increased during therapy. The largest effect of therapy was on triglycerides, which increased an average of 45% in the SHR patients from baseline to wk 7, when the patients received asparaginase but not dex in the preceding 2 wks. From wk 7 to 8, triglycerides increased 59% in LR and 72% in the SHR arm, after one wk of dex and asparaginase. Although hypertriglyceridemia developed in a majority (52%) of patients, it was not associated with pancreatitis, which occurred in six patients. The increase in triglycerides from baseline to wk 7 in SHR patients was related to older age (p=0.0001) and decrease in serum albumin (p=6.6 x 10-5).The additional increase in triglycerides from wk 7 to 8 was related to dex PK (p=0.08).

We conclude that both asparaginase and dex are likely to contribute to changes in serum lipids based on the timing of the changes in the serum lipids relative to therapy and the associations with asparaginase biomarkers and dex PK. Furthermore, these data suggest that asparaginase had a larger effect than dex on these changes and that the largest changes were in serum triglycerides.

Lipid measurements during therapyBaseline (CONS D15)CONT W7CONT W8CONT W12MedianQuartilesMedianQuartilesMedianQuartilesMedianQuartilesAlbumin (SHR)4.13.9-4.43.2***###2.8-3.73.3###2.9-3.93.0***###2.6-3.4Albumin (LR)4.24.0-4.44.24.0-4.43.8***3.5-4.14.1***3.8-4.3LDL (SHR)8664-10970***##51-9579.5*###60-10669###49-108LDL (LR)8059-938768-10561***43-81100***78-125.5HDL (SHR)47.538.2-56.349.336.3-60.641.3*25.3-60.543.1##28.9-56.8HDL (LR)45.539.9-55.152.443.7-62.144.5***31.3-57.653.7***43-64.1TRI (SHR)8962-130129***###87-198222***###113-519134***##80-267TRI (LR)9164-1406452-86102***72-16595*71-129CHOL (SHR)150128-171150.5128-177183.5***###146-231155.5#122-213CHOL (LR)142120-160148125-169132109-154171***143-199CONS, Consolidation phase. CONT, continuation phase. LR, low risk treatment group; SHR, standard/high risk treatment group; LDL, low density lipoprotein; HDL, high density lipoprotein; TRI, triglycerides; CHOL, total cholesterol; All units in mg/dL.*, p&lt;0.05 compared to prior measurement; **, p&lt;0.001 compared to prior measurement; ***, p&lt;10-5 compared to prior measurement (paired Wilcoxon test, adjusted for age, gender, and race)#, p&lt;0.05 compared to LR group; ##, p&lt;0.001 compared to LR group; ###, p&lt;10-5 compared to LR group (Kruskal-Wallis test, adjusted for age, gender, and race)

Citation Format: Laura B. Ramsey, Katherine M. Robinson, Jitesh D. Kawedia, Wenjian Yang, Chengcheng Liu, John C. Panetta, Sima Jeha, Deepa Bhojwani, Monika L. Metzger, Cheng Cheng, William E. Evans, Ching-Hon Pui, Mary V. Relling. Dexamethasone (dex) and asparaginase increase triglycerides during acute lymphoblastic leukemia (ALL) therapy in children. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT409. doi:10.1158/1538-7445.AM2014-CT409