High incidence of symptomatic hyperammonemia in children with acute lymphoblastic leukemia receiving pegylated asparaginase

Research output: Chapter in Book/Report/Conference proceedingBook chapter

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High incidence of symptomatic hyperammonemia in children with acute lymphoblastic leukemia receiving pegylated asparaginase. / Heitink-Pollé, Katja M.J.; Prinsen, Berthil H.C.M.T.; de Koning, Tom J.; van Hasselt, Peter M.; Bierings, Marc B.

JIMD Reports. Springer Gabler, 2013. p. 103-108 (JIMD Reports; Vol. 7).

Research output: Chapter in Book/Report/Conference proceedingBook chapter

Harvard

Heitink-Pollé, KMJ, Prinsen, BHCMT, de Koning, TJ, van Hasselt, PM & Bierings, MB 2013, High incidence of symptomatic hyperammonemia in children with acute lymphoblastic leukemia receiving pegylated asparaginase. in JIMD Reports. JIMD Reports, vol. 7, Springer Gabler, pp. 103-108. https://doi.org/10.1007/8904_2012_156

APA

Heitink-Pollé, K. M. J., Prinsen, B. H. C. M. T., de Koning, T. J., van Hasselt, P. M., & Bierings, M. B. (2013). High incidence of symptomatic hyperammonemia in children with acute lymphoblastic leukemia receiving pegylated asparaginase. In JIMD Reports (pp. 103-108). (JIMD Reports; Vol. 7). Springer Gabler. https://doi.org/10.1007/8904_2012_156

CBE

Heitink-Pollé KMJ, Prinsen BHCMT, de Koning TJ, van Hasselt PM, Bierings MB. 2013. High incidence of symptomatic hyperammonemia in children with acute lymphoblastic leukemia receiving pegylated asparaginase. In JIMD Reports. Springer Gabler. pp. 103-108. (JIMD Reports). https://doi.org/10.1007/8904_2012_156

MLA

Vancouver

Heitink-Pollé KMJ, Prinsen BHCMT, de Koning TJ, van Hasselt PM, Bierings MB. High incidence of symptomatic hyperammonemia in children with acute lymphoblastic leukemia receiving pegylated asparaginase. In JIMD Reports. Springer Gabler. 2013. p. 103-108. (JIMD Reports). https://doi.org/10.1007/8904_2012_156

Author

Heitink-Pollé, Katja M.J. ; Prinsen, Berthil H.C.M.T. ; de Koning, Tom J. ; van Hasselt, Peter M. ; Bierings, Marc B. / High incidence of symptomatic hyperammonemia in children with acute lymphoblastic leukemia receiving pegylated asparaginase. JIMD Reports. Springer Gabler, 2013. pp. 103-108 (JIMD Reports).

RIS

TY - CHAP

T1 - High incidence of symptomatic hyperammonemia in children with acute lymphoblastic leukemia receiving pegylated asparaginase

AU - Heitink-Pollé, Katja M.J.

AU - Prinsen, Berthil H.C.M.T.

AU - de Koning, Tom J.

AU - van Hasselt, Peter M.

AU - Bierings, Marc B.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Asparaginase is a mainstay of treatment of childhood acute lymphoblastic leukemia. Pegylation of asparaginase extends its biological half-life and has been introduced in the newest treatment protocols aiming to further increase treatment success. Hyperammonemia is a recognized side effect of asparaginase treatment, but little is known about its incidence and clinical relevance. Alerted by a patient with severe hyperammonemia after introduction of the new acute lymphoblastic leukemia protocol, we analyzed blood samples and clinical data of eight consecutive patients receiving pegylated asparaginase (PEG-asparaginase) during their treatment of acute lymphoblastic leukemia. All patients showed hyperammonemia (>50 μmol/L) and seven patients (88 %) showed ammonia concentrations > 100 μmol/L. Maximum ammonia concentrations ranged from 89 to 400 μmol/L. Symptoms varied from mild anorexia and nausea to headache, vomiting, dizziness, and lethargy and led to early interruption of PEG-asparaginase in three patients. No evidence of urea cycle malfunction was found, so overproduction of ammonia through hydrolysis of plasma asparagine and glutamine seems to be the main cause. Interestingly, ammonia concentrations correlated with triglyceride values (r = 0.68, p < 0.0001), suggesting increased overall toxicity. The prolonged half-life of PEG-asparaginase may be responsible for the high incidence of hyperammonemia and warrants future studies to define optimal dosing schedules based on ammonia concentrations and individual asparagine and asparaginase measurements.

AB - Asparaginase is a mainstay of treatment of childhood acute lymphoblastic leukemia. Pegylation of asparaginase extends its biological half-life and has been introduced in the newest treatment protocols aiming to further increase treatment success. Hyperammonemia is a recognized side effect of asparaginase treatment, but little is known about its incidence and clinical relevance. Alerted by a patient with severe hyperammonemia after introduction of the new acute lymphoblastic leukemia protocol, we analyzed blood samples and clinical data of eight consecutive patients receiving pegylated asparaginase (PEG-asparaginase) during their treatment of acute lymphoblastic leukemia. All patients showed hyperammonemia (>50 μmol/L) and seven patients (88 %) showed ammonia concentrations > 100 μmol/L. Maximum ammonia concentrations ranged from 89 to 400 μmol/L. Symptoms varied from mild anorexia and nausea to headache, vomiting, dizziness, and lethargy and led to early interruption of PEG-asparaginase in three patients. No evidence of urea cycle malfunction was found, so overproduction of ammonia through hydrolysis of plasma asparagine and glutamine seems to be the main cause. Interestingly, ammonia concentrations correlated with triglyceride values (r = 0.68, p < 0.0001), suggesting increased overall toxicity. The prolonged half-life of PEG-asparaginase may be responsible for the high incidence of hyperammonemia and warrants future studies to define optimal dosing schedules based on ammonia concentrations and individual asparagine and asparaginase measurements.

KW - Acute lymphoblastic leukemia

KW - Ammonia concentration

KW - Orotic acid

KW - Plasma amino acid

KW - Urea cycle

UR - http://www.scopus.com/inward/record.url?scp=85055051620&partnerID=8YFLogxK

U2 - 10.1007/8904_2012_156

DO - 10.1007/8904_2012_156

M3 - Book chapter

AN - SCOPUS:85055051620

T3 - JIMD Reports

SP - 103

EP - 108

BT - JIMD Reports

PB - Springer Gabler

ER -