Prevention and management of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: Recommendations of an expert panel

University of Chicago, Chicago, IL, USA.
Leukemia & lymphoma (Impact Factor: 2.89). 08/2011; 52(12):2237-53. DOI: 10.3109/10428194.2011.596963
Source: PubMed

ABSTRACT The rapidly increasing use of pegasparaginase (pegASNase) in adults, after a half century of use of asparaginase (ASNase) in children, has prompted a need for guidelines in the management and prevention of toxicities of asparagine depletion in adults. Accordingly, an initial set of recommendations are provided herein. Major advantages of pegASNase are its 2-3-week duration of action, in contrast to less than 3 days with native ASNase, and the flexibility of intravenous or intramuscular administration of pegASNase and associated patient and physician convenience. The most frequent toxicities of both types of ASNase are hepatic and pancreatic, with pancreatitis being the most serious. Other toxicities are hypersensitivity reactions, thrombosis, nausea/vomiting, and fatigue. Whether or not the replacement of one dose of pegASNase for 6-9 doses of native ASNase can be achieved in adults with similar efficacy and acceptable toxicities to those achieved in children remains to be established.

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    • "Previous studies have reported that L-asparaginase (L-Asp)-based regimens may be an effective option to improve the chemotherapeutic efficacy on ENKTL (1–3). Acute pancreatitis is one of the predominant toxicities that is associated with L-Asp therapy (4). In the present study, a case of lethal L-Asp-associated pancreatitis (AAP) in an adult patient with ENKTL is presented, to raise awareness regarding the severe side-effects of L-Asp and the potential risk factors for developing lethal AAP in adults. "
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    ABSTRACT: L-asparaginase (L-Asp)-associated pancreatitis (AAP) occurs occasionally; however, this side-effect has predominantly been observed among pediatric patients. Usually, it is not life-threatening and generally responds to intensive medical therapy. The present study presents a rare case of lethal AAP in an adult. The patient was recently diagnosed with extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, and the chronic hepatitis B virus (HBV) infection and was receiving L-Asp as part of a chemotherapy regimen. Severe acute pancreatitis occurred and the patient succumbed 72 h after completion of chemotherapy. The HBV infection and lipid disorders may have been potential risk factors for the development of severe acute pancreatitis in the patient.
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    • "Generally, triglyceride levels are lowered significantly in a few days, but the efficacy of these approaches have not been formally evaluated (Dietel et al, 2007; Kfoury-Baz et al, 2008; Ridola et al, 2008; Solano-Paez et al, 2011). For adolescent and adult patient with asparaginase-associated hypertriglyceridaemia above 11Á3 mmol/l, but without pancreatitis , it is recommended that such patients should be followed closely for pancreatitis, and that L-asparaginase therapy should be withheld until triglyceride levels have normalized (Stock et al, 2011). However, such expert panel recommendations are not available for children. "
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    ABSTRACT: l-asparaginase has been an element in the treatment for acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma since the late 1960s and remains an essential component of their combination chemotherapy. Among the major toxicities associated with l-asparaginase therapy are pancreatitis, allergic reactions, thrombotic events, hepatotoxicity and hyperlipidaemia. Acute pancreatitis is one of the most common reasons for stopping treatment with l-asparaginase. Short-term complications of asparaginase-associated pancreatitis include development of pseudocysts and pancreatic necrosis. Long-term complications include chronic pancreatitis and diabetes. The pathophysiology of asparaginase-associated pancreatitis remains to be uncovered. Individual clinical and genetic risk factors have been identified, but they are only weak predictors of pancreatitis. This review explores the definition, possible risk factors, treatment and complications of asparaginase-associated pancreatitis.
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