The goal of this manuscript is to review the clinical evidence linking asparaginase activity levels to outcomes in patients with ALL and to provide an overview of how asparaginase activity levels may be used to guide treatment.
Our work establishes a powerful strategy for further exploitation of the human asparaginase sequence space to facilitate the identification of in vitro-evolved enzyme species that will lay the basis for improved ALL therapy.
Crisantaspase is an asparaginase enzyme produced by Erwinia chrysanthemi and used to treat acute lymphoblastic leukemia (ALL) in case of hypersensitivity to Escherichia coli l-asparaginase (ASNase).
Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients.
Erwinia asparaginase is a Food and Drug Administration approved agent for the treatment of acute lymphoblastic leukemia (ALL) for patients who develop hypersensitivity to Escherichia coli derived asparaginases.
Thirty-six adults with acute lymphoblastic leukemia (ALL) were treated with adriamycin, vincristine, prednisolone, and asparaginase for remission induction, followed by vincristine-adriamycin-cyclophosphamide consolidation courses, cranial irradiation, a short ara-C plus VM-26 pulse, and vincristine plus cyclophosphamide rotating weekly with ara-C plus VM-26 for three months (reinforced HEAV'D).
Not only do these studies offer the possibility for investigating the kinetic behavior of biochemically interesting mammalian AS mutants, but such ready access to large amounts of enzyme also represents a major step in the development and characterization of inhibitors that might have clinical utility in treating asparaginase-resistant ALL.
The etiology for his hyperglycemia was most likely a result of oral glucocorticoid therapy combined with asparaginase therapy-both are a cornerstone of induction chemotherapy for ALL.
In study XV, the level of residual disease was used to guide treatment, which featured intensive methotrexate, glucocorticoid, vincristine, and asparaginase, as well as early triple intrathecal therapy for higher-risk ALL.
In this retrospective analysis, short-acting L-asparaginase (L-ASP) and long-acting polyethylene glycol (PEG)-asparaginase (PEG-ASP) were compared for grade 3-4 toxicities and characterized by patient and drug-related factors to identify strategies for toxicity avoidance in adults with ALL.
Pancreatitis is a frequent toxicity to acute lymphoblastic leukemia (ALL) treatment, significantly associated with asparaginase use, and may be followed by severe complications such as acute hyperglycaemia, need for mechanical ventilation, pseudocysts, and death.
Here, we sought to determine a potential association between the variant rs4880 in SOD2 gene, a key mitochondrial enzyme that protects cells against ROS, and hepatotoxicity during asparaginase-based therapy in 224 patients enrolled on CALGB-10102, a treatment trial for adults with ALL.
Ability to administer full-dose LMWH, expected bleeding rate, and completion of asparaginase doses while on ACT suggest full-dose ACT is feasible and safe in children with ALL/LL who develop TE during DFCI ALL consortium therapy protocols.
In this systematic review, older age, asparaginase formulation, higher ALL risk stratification, and higher asparaginase dosing appear to play a limited role in the development of AAP.
These results provide what we believe to be a new basis for understanding asparaginase resistance in ALL and indicate that MSC niches in the bone marrow can form a safe haven for leukemic cells.
Similar genome-wide approaches have also discovered novel germline genetic risk factors that independently influence ALL prognosis and those that strongly modify host susceptibility to adverse effects of antileukemic agents (eg, vincristine, asparaginase, glucocorticoids).
A 13-year-old girl with acute lymphoblastic leukemia (ALL) developed extremely high plasma triglyceride (TG) concentrations of 103 mmol/l (reference value <1.8 mmol/l) during combination treatment with corticosteroids and asparaginase.
Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored.
This study provides pilot data for a future randomized trial of the use of LMWH during ALL therapy for the prevention of asparaginase-associated thrombotic events.