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).
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.
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.
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.
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.
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.
Assays with IGFBP7 knockdown ALL and stromal cell lines, or with addition of recombinant rIGFBP7 (rIGFBP7) to the culture medium, showed that IGFBP7 acts as a positive regulator of ALL and stromal cells growth, and significantly enhances in-vitro resistance of ALL to asparaginase.
Our objective was to use a genome-wide approach to identify loci associated with asparaginase hypersensitivity in children with ALL enrolled on St. Jude Children's Research Hospital (SJCRH) protocols Total XIIIA (n = 154), Total XV (n = 498), and Total XVI (n = 271), or Children's Oncology Group protocols POG 9906 (n = 222) and AALL0232 (n = 2163).
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).
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.
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.
In this paper, we will review the differences in pharmacokinetics and toxicities, when asparaginase is administered intravenously versus intramuscularly in pediatric patients with ALL.
A phase I/II study of Erwinia asparaginase in Japanese children and young adults with acute lymphoblastic leukemia (ALL) was performed to investigate its activity and toxicity.
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.
Erwinia asparaginase, a bacteria-derived enzyme drug, has been used in the treatment of various cancers, especially acute lymphoblastic leukemia (ALL).
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.
Patients between 1 and 19 years of age with primary ALL, who are treated within the Dutch Childhood Oncology Group (DCOG) ALL-11 or 12 study will be randomized to thromboprophylaxis with LMWH once daily, (dose of 85 IU/kg (intervention arm A)), or to no thromboprophylaxis (arm B, standard of care) during asparaginase courses of ALL treatment.
Asparaginase, a cornerstone of modern pediatric chemotherapy regimens for ALL and asparaginase-containing protocols, is increasingly used in adolescent and adult patients historically treated with asparaginase-free regimens..
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.
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.
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.