Dataset Information

Erythrocyte encapsulated l-asparaginase (GRASPA) in acute leukemia.

ABSTRACT: l-asparaginase, an enzyme originally derived from Escherichia coli, represents a major drug in the treatment of acute lymphoblastic leukemia. However, the occurrence of major adverse effects often leads to early withdrawal of the enzyme. Main side effects include immune-allergic reactions, coagulopathy, pancreatitis and hepatic disorders. Novel asparaginase formulations and alternative sources have been developed to address this issue, but the results were not totally satisfactory. l-asparaginase loaded red blood cells (RBCs; GRASPA) represent a new asparaginase presentation with reduced immunological adverse reactions. RBCs protect l-asparaginase, enhance its half-life and reduce the occurrence of adverse events. We reviewed the history, biology and clinical experiences with l-asparaginase, and the characteristics and first clinical experiences with GRASPA in the treatment of acute leukemia.

SUBMITTER: Thomas X

PROVIDER: S-EPMC6172001 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Erythrocyte encapsulated l-asparaginase (GRASPA) in acute leukemia.

Thomas Xavier X Le Jeune Caroline C

International journal of hematologic oncology 20160505 1

l-asparaginase, an enzyme originally derived from <i>Escherichia coli</i>, represents a major drug in the treatment of acute lymphoblastic leukemia. However, the occurrence of major adverse effects often leads to early withdrawal of the enzyme. Main side effects include immune-allergic reactions, coagulopathy, pancreatitis and hepatic disorders. Novel asparaginase formulations and alternative sources have been developed to address this issue, but the results were not totally satisfactory. l-aspa ...[more]

PMID: 30302200

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Project description:BackgroundGlucocorticoids 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).ProcedurePatients 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.ResultsThe 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).ConclusionTriglycerides 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.

Dataset Information

Erythrocyte encapsulated l-asparaginase (GRASPA) in acute leukemia.

Publications

Erythrocyte encapsulated l-asparaginase (GRASPA) in acute leukemia.

Similar Datasets

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