Cerebral vein thrombosis (1.7%) occurred in two pediatric patients; 2.4% (43/1795) of pediatric patients and 4.9% (72/1486) of adult patients suffered from VTE, respectively; 2.7% (56/2064) of ALL and 4.9% (59/1217) of lymphoma patients were diagnosed with VTE after L-asp exposure.
On the basis of the data suggesting that adolescents and young adult patients with acute lymphoblastic leukemia (ALL) have improved outcomes when treated on pediatric protocols, we assessed the feasibility of treating adult patients aged 18-50 years with ALL with the DFCI Pediatric ALL Consortium regimen utilizing a 30-week course of pharmacokinetically dose-adjusted E. coli L-asparaginase during consolidation.
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).
We first tested acute lymphoblastic leukemia (ALL) cells and showed that treatment with GCN2 inhibitors rendered ALL cells sensitive to ASNase by preventing the induction of ASNS, resulting in reduced levels of de novo protein synthesis.
Thus, the aim of the present phase II study was to test a pediatric-inspired treatment, including intensified doses of nonmyelotoxic drugs, such as prednisone, vincristine, or L-asparaginase, in adult patients with ALL up to the age of 60 years.
L-asparaginase (ASNase) from Escherichia coli is currently used in some countries in its PEGylated form (ONCASPAR, pegaspargase) to treat acute lymphoblastic leukemia (ALL).
Fibrinogen, von Willebrand factor antigen (VWF:Ag), total protein, and albumin levels as well as antithrombin (AT) and L-asparaginase activities were measured in 97 children with ALL treated for prolonged period of time with L-asparaginase.
Underlying the lack of prognostic significance, we found that the chemotherapy agents used in our cohort (vincristine, L-asparaginase, and methotrexate) were each able to induce ALL cell death in a BIM-independent fashion, and resensitize BIM deletion-containing cells to GCs.
Our results revealed that curcumin significantly enhanced the antitumor effect of L-ASP in the three ALL cell lines compared to that for L-ASP alone ( p < 0.05).
The reported incidence of thromboembolism in children with acute lymphoblastic leukemia (ALL) treated with L-asparaginase, vincristine, and prednisone varies from 2.4% to 11.5%.
L-asparaginase is an enzyme produced by microorganisms, plants, and animals, which is used clinically for the treatment for acute lymphoblastic leukemia (ALL) and, in the food industry, to control acrylamide formation in baked foods.
The soil metagenome derived L-asparaginase with enhanced activities could be a potential candidate to develop as a drug in Acute Lymphoblastic Leukemia (ALL) therapy.
L-asparaginase (L-Asp)-associated thromboembolisms are serious complications in pediatrics patients with acute lymphoblastic leukemia (ALL), especially at ≥10.0 years old, but the pathogenesis remains to be clarified.
However, patients often relapse because of the development of resistance, but the underlying mechanism of ALL cell resistance to l-asparaginase remains unknown.
Acute lymphoblastic leukemia (ALL) cells are sensitive to asparagine depletion, and administration of the asparagine depletion enzyme l-asparaginase is an important therapy option.
Here we show that novel low l-glutaminase variants developed on the backbone of the FDA-approved <i>Erwinia chrysanthemi</i> l-asparaginase were highly efficacious against both T- and B-cell ALL, while displaying reduced acute toxicity features.