Contributions
Abstract: EP362
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
PEG-asparaginase, a long-acting formulation of L-asparaginase, is used as part of treatment protocols for Philadelphia negative acute lymphoblastic leukemia (ALL). In pediatric studies, triglycerides were more affected by PEG asparaginase compared to native L-asparaginase (10.0% vs 5.5%). Using PEG asparaginase for ALL was associated with a higher incidence of hypertriglyceridemia up to 50% in adult patients. The clinical significance of this and if re-challenging these patients is safe or not is not clear.
Aims
We sought to determine the safety of re-challenging adult patients with PEG asparaginase after experiencing an episode of severe hypertriglyceridemia (> 1000mg/dl or 11.4mmol/L).
Methods
At Princess Margaret Cancer Center, we recently switched from native E. coli asparaginase to PEG asparaginase using modified pediatric Dana Farber Cancer Institute (DFCI) protocols. 46 consecutive adult patients received PEG-asparaginase as part of DFCI protocol for first-line treatment of Philadelphia negative ALL between February 2020 and December 2020. We analyzed the incidence of hypertriglyceridemia and their subsequent outcomes.
Results
The median age of the patients was 38 years, and 17 (36.9%) were female. 11 patients out of 46 (23.9%) have elevated triglycerides with levels above 2.2mmol/L. Elevated triglycerides occurred a median of 2 weeks after initial treatment; 4 out of 46 patients had severe hypertriglyceridemia with levels above 11.4 mmol/L (8.7%). The management of these patients was supportive in the form of a low-fat diet, hydration and fenofibrate or gemfibrozil. Their next treatment cycle with PEG-asparaginase was delayed by two weeks on average (range 1-3) until normalizing their triglycerides level. None of these patients required plasmapheresis or insulin infusion as a treatment for hypertriglyceridemia. Only one of 11 patients (9%) developed acute pancreatitis after the second cycle of intensification; he had severe hypertriglyceridemia with the first intensification cycle and proceeded to the next cycle before normalizing the triglyceride. This patient did not re-challenge subsequently with PEG-asparaginase. The remaining ten patients were re-challenged after dropping triglyceride levels without developing pancreatitis. Among the 4 patients with severe hypertriglyceridemia, two completed their intensification phase therapy with PEG asparaginase. One patient continues to receive PEG asparaginase as part of the intensification treatment and one patient was not re-challenged as he developed acute pancreatitis as mentioned above.
Three patients with severe hypertriglyceridemia were noted to have high anion gap metabolic acidosis with hypobicarbonatemia and or hyperammonemia. This was normal on repeat testing using venous blood gas and testing with an alternative device for ammonia. The evaluation revealed that the low bicarbonate level was fictitious and was related to lipemic serum.
Conclusion
With moving from native asparaginase to PEG asparaginase in adult patients with ALL, hypertriglyceridemia incidence was high. Checking triglycerides at baseline and monitoring levels while receiving PEG asparaginase is needed to safely receive their treatment on subsequent cycles after the initial PEG asparaginase exposure. In patients with hypertriglyceridemia not complicated by acute pancreatitis, re-challenging these patients who did not have pancreatitis is safe once the triglycerides level normalizes.
Keyword(s): Acute lymphoblastic leukemia, Asparaginase
Abstract: EP362
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
PEG-asparaginase, a long-acting formulation of L-asparaginase, is used as part of treatment protocols for Philadelphia negative acute lymphoblastic leukemia (ALL). In pediatric studies, triglycerides were more affected by PEG asparaginase compared to native L-asparaginase (10.0% vs 5.5%). Using PEG asparaginase for ALL was associated with a higher incidence of hypertriglyceridemia up to 50% in adult patients. The clinical significance of this and if re-challenging these patients is safe or not is not clear.
Aims
We sought to determine the safety of re-challenging adult patients with PEG asparaginase after experiencing an episode of severe hypertriglyceridemia (> 1000mg/dl or 11.4mmol/L).
Methods
At Princess Margaret Cancer Center, we recently switched from native E. coli asparaginase to PEG asparaginase using modified pediatric Dana Farber Cancer Institute (DFCI) protocols. 46 consecutive adult patients received PEG-asparaginase as part of DFCI protocol for first-line treatment of Philadelphia negative ALL between February 2020 and December 2020. We analyzed the incidence of hypertriglyceridemia and their subsequent outcomes.
Results
The median age of the patients was 38 years, and 17 (36.9%) were female. 11 patients out of 46 (23.9%) have elevated triglycerides with levels above 2.2mmol/L. Elevated triglycerides occurred a median of 2 weeks after initial treatment; 4 out of 46 patients had severe hypertriglyceridemia with levels above 11.4 mmol/L (8.7%). The management of these patients was supportive in the form of a low-fat diet, hydration and fenofibrate or gemfibrozil. Their next treatment cycle with PEG-asparaginase was delayed by two weeks on average (range 1-3) until normalizing their triglycerides level. None of these patients required plasmapheresis or insulin infusion as a treatment for hypertriglyceridemia. Only one of 11 patients (9%) developed acute pancreatitis after the second cycle of intensification; he had severe hypertriglyceridemia with the first intensification cycle and proceeded to the next cycle before normalizing the triglyceride. This patient did not re-challenge subsequently with PEG-asparaginase. The remaining ten patients were re-challenged after dropping triglyceride levels without developing pancreatitis. Among the 4 patients with severe hypertriglyceridemia, two completed their intensification phase therapy with PEG asparaginase. One patient continues to receive PEG asparaginase as part of the intensification treatment and one patient was not re-challenged as he developed acute pancreatitis as mentioned above.
Three patients with severe hypertriglyceridemia were noted to have high anion gap metabolic acidosis with hypobicarbonatemia and or hyperammonemia. This was normal on repeat testing using venous blood gas and testing with an alternative device for ammonia. The evaluation revealed that the low bicarbonate level was fictitious and was related to lipemic serum.
Conclusion
With moving from native asparaginase to PEG asparaginase in adult patients with ALL, hypertriglyceridemia incidence was high. Checking triglycerides at baseline and monitoring levels while receiving PEG asparaginase is needed to safely receive their treatment on subsequent cycles after the initial PEG asparaginase exposure. In patients with hypertriglyceridemia not complicated by acute pancreatitis, re-challenging these patients who did not have pancreatitis is safe once the triglycerides level normalizes.
Keyword(s): Acute lymphoblastic leukemia, Asparaginase