Asparaginase‐associated pancreatitis is not predicted by hypertriglyceridemia or pancreatic enzyme levels in children with acute lymphoblastic leukemia

Raja, Raheel Altaf; Schmiegelow, Kjeld; Sørensen, Ditte; Frandsen, Thomas Leth

doi:10.1002/pbc.26183

Cited by 24 publications

(22 citation statements)

References 33 publications

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“…How elevated lipids in general, or following asparaginase and dexamethasone therapy, affect this mechanism is unknown. We have previously investigated whether patients with pancreatitis (n = 7) had higher levels of triglycerides than controls (n = 24) and found no association between triglycerides and pancreatitis . However, lack of power in this study could lead to type 1 error.…”

Section: Baseline Characteristics and Cumulative Incidences Of Pancrementioning

confidence: 81%

“…published in this journal that obesity in children with ALL was associated with risk of pancreatitis . Since obesity is an increasing global health issue, hypertriglyceridemia is a risk factor for pancreatitis in non‐ALL adults, and obesity and triglyceride levels are correlated, an association seems plausible, although a recent study failed to demonstrate hypertriglyceridemia as a risk for pancreatitis in children with ALL . Therefore, we aimed to reproduce this association and improve the understanding of risk factors for pancreatitis in childhood ALL.…”

Section: Baseline Characteristics and Cumulative Incidences Of Pancrementioning

confidence: 99%

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Association between body mass index and pancreatitis in children with acute lymphoblastic leukemia

Mogensen

Wolthers

Grell

et al. 2018

Pediatric Blood & Cancer

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Section: Baseline Characteristics and Cumulative Incidences Of Pancrementioning

confidence: 81%

Section: Baseline Characteristics and Cumulative Incidences Of Pancrementioning

confidence: 99%

Association between body mass index and pancreatitis in children with acute lymphoblastic leukemia

Mogensen

Wolthers

Grell

et al. 2018

Pediatric Blood & Cancer

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“…In adults with non-malignant disorders, hypertriglyceridemia (above 10 times the UNL) has been associated with an increased risk of acute pancreatitis 185, 188, 190 , but so far this has not been replicated in children with ALL 191 . A few studies have indicated associations with development of ON and thrombosis 78, 83, 95, 158, 188, 192 , but no randomized studies have explored whether lipid-lowering interventions prevent these complications.…”

Section: Hyperlipidemiamentioning

confidence: 99%

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

et al. 2017

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During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.

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“…The association between hypertriglyceridemia and other toxicities (thrombosis, osteonecrosis, and pancreatitis) has been previously studied. 6,[14][15][16][17] It has been suggested that hypertriglyceridemia may be associated with osteonecrosis and thrombosis, although the associations were not maintained in multivariate analyses. 6 However, there are few large-scale studies to support hypertriglyceridemia as an independent risk factor.…”

Section: Introductionmentioning

confidence: 99%

Asparaginase formulation impacts hypertriglyceridemia during therapy for acute lymphoblastic leukemia

Finch

Smith

Yang

et al. 2019

Pediatric Blood & Cancer

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Background Glucocorticoids and asparaginase, used to treat acute lymphoblastic leukemia (ALL), can cause hypertriglyceridemia. We compared triglyceride levels, risk factors, and associated toxicities in two ALL trials at St. Jude Children's Research Hospital with identical glucocorticoid regimens, but different asparaginase formulations. In Total XV (TXV), native Escherichia coli l‐asparaginase was front‐line therapy versus the pegylated formulation (PEG‐asparaginase) in Total XVI (TXVI). Procedure Patients enrolled on TXV (n = 498) and TXVI (n = 598) were assigned to low‐risk (LR) or standard/high‐risk (SHR) treatment arms (ClinicalTrials.gov identifiers: NCT00137111 and NCT00549848). Triglycerides were measured four times and were evaluable in 925 patients (TXV: n = 362; TXVI: n = 563). The genetic contribution was assessed using a triglyceride polygenic risk score (triglyceride‐PRS). Osteonecrosis, thrombosis, and pancreatitis were prospectively graded. Results The largest increase in triglycerides occurred in TXVI SHR patients treated with dexamethasone and PEG‐asparaginase (4.5‐fold increase; P <1 × 10−15). SHR patients treated with PEG‐asparaginase (TXVI) had more severe hypertriglyceridemia (>1000 mg/dL) compared to native l‐asparaginase (TXV): 10.5% versus 5.5%, respectively (P = .007). At week 7, triglycerides did not increase with dexamethasone treatment alone (LR patients) but did increase with dexamethasone plus asparaginase (SHR patients). The variability in triglycerides explained by the triglyceride‐PRS was highest at baseline and declined with therapy. Hypertriglyceridemia was associated with osteonecrosis (P = .0006) and thrombosis (P = .005), but not pancreatitis (P = .4). Conclusion Triglycerides were affected more by PEG‐asparaginase than native l‐asparaginase, by asparaginase more than dexamethasone, and by drug effects more than genetics. It is not clear whether triglycerides contribute to thrombosis and osteonecrosis or are biomarkers of the toxicities.

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Asparaginase‐associated pancreatitis is not predicted by hypertriglyceridemia or pancreatic enzyme levels in children with acute lymphoblastic leukemia

Abstract: AAP does not seem to be associated with HTG. Continuous monitoring of pancreas enzymes does not predict AAP.

Cited by 24 publications

References 33 publications

Association between body mass index and pancreatitis in children with acute lymphoblastic leukemia

Association between body mass index and pancreatitis in children with acute lymphoblastic leukemia

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

Asparaginase formulation impacts hypertriglyceridemia during therapy for acute lymphoblastic leukemia

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