CALGB 9511 used pegaspargase (PEG-ASP) in lieu of the native enzyme. The aim was to compare differences in overall survival (OS) and disease-free survival (DFS) between patients who did and did not achieve asparagine depletion, defined by enzyme levels greater than 0.03 U/mL plasma for 14 consecutive days after at least 1 of 4 planned PEG-ASP administrations. Samples were available from 85 eligible patients. On univariate analyses, the 22 patients who did not achieve asparagine depletion had inferior OS (P = .002; hazard ratio [HR] = 2.37; 95% CI = 1.38-4.09) and DFS (P = .012; HR = 2.21; 95% CI = 1.19-4.13). After adjusting for age, performance status, leukocyte count, and karyotype in a proportional hazards model, both the OS and DFS HRs decreased to 1.8 (P = .056; 95% CI = 1.0-3.2 and P = .084; 95% CI = 0.9-3.6, respectively). We conclude that effective asparagine depletion with PEG-ASP is feasible as part of an intensive multiagent therapeutic regimen in adult acute lymphoblastic leukemia and appears associated with improved outcomes.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885493 | PMC |
http://dx.doi.org/10.1182/blood-2006-09-045351 | DOI Listing |
Bioconjug Chem
January 2025
Department of Biochemistry, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Torun, ul. Lwowska 1, 87-100 Torun, Poland.
l-Asparaginase (l-ASNase) catalyzes the hydrolysis of l-asparagine, leading to its depletion and subsequent effects on the cellular proliferation and survival. In contrast to normal cells, malignant cells that lack asparagine synthase are extremely susceptible to asparagine deficiency. l-ASNase has been successfully employed in treating pediatric leukemias and non-Hodgkin lymphomas; however, its usage in adult patients and other types of cancer is limited due to significant side effects and drug resistance.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Parkinson's disease (PD) is characterized by the deposition of misfolded α-synuclein (α-syn) in the brain. Converging evidence indicates that the intracellular transmission and subsequent templated amplification of α-syn are involved in the onset and progression of PD. However, the molecular mechanisms underlying the cell-to-cell transmission of pathological α-syn remain poorly understood.
View Article and Find Full Text PDFHeliyon
December 2024
State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guian New Disctrict, 561113, Guizhou, PR China.
Metabolic reprogramming is a crucial characteristic of cancer, allowing cancer cells to acquire metabolic properties that support their survival, immune evasion, and uncontrolled proliferation. Consequently, targeting cancer metabolism has become an essential therapeutic strategy. Abnormal amino acid metabolism is not only a key aspect of metabolic reprogramming but also plays a significant role in chemotherapy resistance and immune evasion, particularly in leukemia.
View Article and Find Full Text PDFNew Phytol
November 2024
LIPME, Université de Toulouse, INRAE, CNRS, 31326, Castanet-Tolosan, France.
Ralstonia pseudosolanacearum, a plant pathogen responsible for bacterial wilt in numerous plant species, exhibits paradoxical growth in the host by achieving high bacterial densities in xylem sap, an environment traditionally considered nutrient-poor. This study combined in vitro experiments and mathematical modeling to elucidate the population dynamics of R. pseudosolanacearum within plants.
View Article and Find Full Text PDFDrug Chem Toxicol
October 2024
Red Latinoamericana de Implementación y Validación de Guías Clínicas Farmacogenómicas (RELIVAF-CYTED), Santiago, Chile.
L-asparaginase (L-Asp) is an essential enzyme in the treatment of patients with Acute Lymphoblastic Leukemia (ALL), commonly associated with adverse events (AE). Knowing the pharmacokinetic and pharmacodynamic (PK/PD) parameters of L-Asp as well as its relationship with the development of AE is an important strategy in the search to improve the efficacy and safety of the treatment. Seventy-four children with ALL that were being treated with L-Asp, were included.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!