Purpose: Asparaginase (ASNase) is an important component of acute lymphoblastic leukemia (ALL) treatment, but is often discontinued because of toxicity. ASNase () substitution was approved in 2011 for allergic reactions. has, however, been intermittently unavailable because of drug supply issues. The impact of substitution or complete ASNase discontinuation is unknown.
Methods: Patients aged 1-30.99 years in frontline Children's Oncology Group trials for B-cell acute lymphoblastic leukemia between 2004 and 2011 (National Cancer Institute [NCI] standard risk [SR]: AALL0331; NCI high risk: AALL0232) were included. The number of prescribed pegaspargase (PEG-ASNase) doses varied by trial and strata. Maintenance therapy did not contain ASNase. Landmark analyses at maintenance compared disease-free survival (DFS) among those receiving all prescribed PEG-ASNase doses versus switching to but receiving all doses versus not receiving all ASNase doses.
Results: We included 5,195 AALL0331 and 3,001 AALL0232 patients. The cumulative incidence of PEG-ASNase discontinuation was 12.2% ± 4.6% in AALL0331 and 25.4% ± 0.8% in AALL0232. In multivariable analyses, NCI high-risk patients not receiving all prescribed ASNase doses had inferior DFS (hazard ratio [HR], 1.5; 95% CI, 1.2 to 1.9; = .002) compared with those receiving all prescribed PEG-ASNase doses. Patients with substitution who completed subsequent courses were not at increased risk (HR, 1.1; 95% CI, 0.7 to 1.6; = .69). NCI SR patients who discontinued ASNase were not at elevated risk (HR, 1.2; 95% CI, 0.9 to 1.6; = .23), except when restricted to those with slow early response, who were prescribed more ASNase because of therapy intensification (HR, 1.7; 95% CI, 1.1 to 2.7; = .03).
Conclusion: Discontinuation of ASNase doses is associated with inferior DFS in higher-risk patients. Our results illustrate the severe consequences of shortages.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280050 | PMC |
| http://dx.doi.org/10.1200/JCO.19.03024 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HOPX as a tumour-suppressive protein in T-cell acute lymphoblastic leukaemia.
Br J Haematol
December 2024
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
The homeodomain protein homeobox (HOPX), a multifaceted regulator of cellular functions and developmental processes, is predominantly expressed in stem cells across diverse tissues; it has also emerged as a tumour suppressor in various solid cancers. However, its role in haematological malignancies still remains undefined. This study aimed to elucidate its significance in T-cell acute lymphoblastic leukaemia (T-ALL).
View Article and Find Full Text PDFB-Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma Mimicking Fibrosing Mediastinitis: A Case Report and Diagnostic Insight.
Am J Case Rep
December 2024
Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan.
BACKGROUND Fibrosing mediastinitis (FM) is a rare, fibroproliferative disorder within the mediastinum. It is extremely rare for hematologic malignancies to develop as FM. CASE REPORT A 32-year-old Japanese man with a 1-month history of headache and 2-week history of facial swelling underwent chest computed tomography (CT); a diffuse mass-like lesion was revealed in the anterior mediastinum with severe stenosis of vital mediastinal organs.
View Article and Find Full Text PDFExtreme hyperleukocytosis (Leukocyte count >200 × 10/L) in an adolescent young adult (AYA) patient with B-ALL could result in mild symptoms of leukostasis. Hyperleukocytosis requires prompt initiation of therapy with adequate hydration, cytoreduction and prevention of tumor lysis. Ph + B-ALL may present with extreme hyperleukocytosis and may be resistant to initial pre-phase therapy.
View Article and Find Full Text PDFEvaluation of methotrexate Pharmacogenomic variation to predict acute neurotoxicity in children with acute lymphoblastic leukemia.
Pharmacotherapy
December 2024
Texas Children's Cancer and Hematology Centers, Houston, Texas, USA.
Background: Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.
Methods: This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States.
Association of B-Lineage Lymphoblastic Leukaemia Gene Polymorphisms with Poor Prognostic Features.
Asian Pac J Cancer Prev
December 2024
Department of Science and Postgraduate Education, Scientific Center of Pediatrics and Pediatric Surgery, Almaty, Republic of Kazakhstan.
Objective: Of this study was to analyse the correlation of gene polymorphisms with clinical and laboratory data of paediatric patients with B-lineage acute lymphoblastic leukaemia with prognostically unfavourable features.
Methods: A study of 200 children with B-lineage acute lymphoblastic leukaemia (B-ALL) treated with polychemotherapy programmes was conducted. Analysis by sex revealed a statistically insignificant predominance of the group of boys over girls (54%).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!