Asparaginase: How to Better Manage Toxicities in Adults

Pourhassan, Hoda; Douer, Dan; Pullarkat, Vinod; Aldoss, Ibrahim

doi:10.1007/s11912-022-01345-6

Cited by 3 publications

(5 citation statements)

References 101 publications

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“…79–82 Complications associated with this disequilibrium are predominantly venous rather than arterial and can include the more rare but particularly serious complication of cerebral venous thrombosis (CVT), which has been reported in 1% to 3% of adults being treated with asparaginase and has been associated with superimposed venous hemorrhage. 80…”

Section: Thrombohemorrhagic Syndrome/thrombosismentioning

confidence: 99%

“…[79][80][81][82] Complications associated with this disequilibrium are predominantly venous rather than arterial and can include the more rare but particularly serious complication of cerebral venous thrombosis (CVT), which has been reported in 1% to 3% of adults being treated with asparaginase and has been associated with superimposed venous hemorrhage. 80 AML has been associated with the presentation of DIC at diagnosis, and this is most prevalent in the APL subtype. 83,84 DIC affects multiple procoagulant and anticoagulant pathways, and therefore presents with both thrombosis and bleeding.…”

Section: Thrombohemorrhagic Syndrome/ Thrombosismentioning

confidence: 99%

“…78 Asparaginase affects hepatic protein synthesis leading to decreases in procoagulant factors (such as fibrinogen, factors II, V, and X), as well as anticoagulants (such as protein C, protein S, plasminogen, and antithrombin), and downregulates fibrinolytic factors (such as plasminogen). [79][80][81][82] Complications associated with this disequilibrium are predominantly venous rather than arterial and can include the more rare but particularly serious complication of cerebral venous thrombosis (CVT), which has been reported in 1% to 3% of adults being treated with asparaginase and has been associated with superimposed venous hemorrhage. 80 AML has been associated with the presentation of DIC at diagnosis, and this is most prevalent in the APL subtype.…”

Section: Thrombohemorrhagic Syndrome/ Thrombosismentioning

confidence: 99%

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Important Considerations in the Intensive Care Management of Acute Leukemias

Pourhassan,

Kareem,

Agrawal

et al. 2023

J Intensive Care Med

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In the realm of hematologic disorders, acute leukemia is approached as an emergent disease given the multitude of complications and challenges that present both as a result of inherent disease pathology and adverse events associated with antineoplastic therapies and interventions. The heavy burden of leukemic cells may lead to complications including tumor lysis syndrome, hyperleukocytosis, leukostasis, and differentiation syndrome, and the initiation of treatment can further exacerbate these effects. Capillary leak syndrome is observed as a result of antineoplastic agents used in acute leukemia, and L-asparaginase, a bacterial-derived enzyme, has a unique side effect profile including association with thrombosis. Thrombohemorrhagic syndrome and malignancy-associated thrombosis are also commonly observed complications due to direct disequilibrium in coagulant and anticoagulant factors. Due to inherent effects on the white blood cell milieu, leukemia patients are inherently immunocompromised and vulnerable to life-threatening sepsis. Lastly, the advents of newer therapies such as chimeric antigen receptor (CAR) T-cells have clinicians facing the management of related toxicities on unfamiliar territory. This review aims to discuss these acute leukemia-associated complications, their pathology, and management recommendations.

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Section: Thrombohemorrhagic Syndrome/thrombosismentioning

confidence: 99%

Section: Thrombohemorrhagic Syndrome/ Thrombosismentioning

confidence: 99%

Section: Thrombohemorrhagic Syndrome/ Thrombosismentioning

confidence: 99%

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Important Considerations in the Intensive Care Management of Acute Leukemias

Pourhassan,

Kareem,

Agrawal

et al. 2023

J Intensive Care Med

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“…Currently, three different approaches are used for enzyme bioengineering: semi-rational, directed evolution, and rational design, depending on the level of information available about the sequence, structure and function of the target enzyme [23]. To improve the various properties of L-ASNases, researchers have used rational design and other molecular approaches [16,[24][25][26][27][28][29][30][31][32][33][34][35][36][37]. Rational design methods have been useful in predicting and modifying enzyme structures.…”

Section: Of 60mentioning

confidence: 99%

Engineering and Expression Strategies for Optimization of L-Asparaginase Development and Production

Shishparenok,

Gladilina,

Zhdanov

2023

IJMS

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Genetic engineering for heterologous expression has advanced in recent years. Model systems such as Escherichia coli, Bacillus subtilis and Pichia pastoris are often used as host microorganisms for the enzymatic production of L-asparaginase, an enzyme widely used in the clinic for the treatment of leukemia and in bakeries for the reduction of acrylamide. Newly developed recombinant L-asparaginase (L-ASNase) may have a low affinity for asparagine, reduced catalytic activity, low stability, and increased glutaminase activity or immunogenicity. Some successful commercial preparations of L-ASNase are now available. Therefore, obtaining novel L-ASNases with improved properties suitable for food or clinical applications remains a challenge. The combination of rational design and/or directed evolution and heterologous expression has been used to create enzymes with desired characteristics. Computer design, combined with other methods, could make it possible to generate mutant libraries of novel L-ASNases without costly and time-consuming efforts. In this review, we summarize the strategies and approaches for obtaining and developing L-ASNase with improved properties.

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“…Toxicities of asparaginase could affect a variety of organ systems, including the liver, and might be severe and prolonged after pegaspargase. However, extracorporeal drug removal has not been included into proposed treatment algorithms of asparaginase toxicities [4]. Only two patients treated with plasmapheresis for asparaginase liver toxicity have been reported [5,6].…”

mentioning

confidence: 99%

Plasmapheresis effectively abrogates severe liver toxicity of pegaspargase in a patient with acute lymphoblastic leukemia

Tölle,

Gökbuget,

Habringer

et al. 2024

Ann Hematol

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Asparaginase: How to Better Manage Toxicities in Adults

Cited by 3 publications

References 101 publications

Important Considerations in the Intensive Care Management of Acute Leukemias

Important Considerations in the Intensive Care Management of Acute Leukemias

Engineering and Expression Strategies for Optimization of L-Asparaginase Development and Production

Plasmapheresis effectively abrogates severe liver toxicity of pegaspargase in a patient with acute lymphoblastic leukemia

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