Purpose: To compare the efficacy and safety of two methotrexate doses and administration schedules in children with anaplastic large-cell lymphoma (ALCL).
Patients And Methods: This randomized trial for children with ALCL was based on the Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Muenster 90 (NHL-BFM90) study protocol and compared six courses of methotrexate 1 g/m2 over 24 hours and an intrathecal injection (IT) followed by folinic acid rescue at 42 hours (MTX1 arm) with six courses of methotrexate 3 g/m2 over 3 hours followed by folinic acid rescue at 24 hours without IT (MTX3 arm). This trial involved most European pediatric/lymphoma study groups and a Japanese group.
Results: Overall, 352 patients (96% ALK positive) were recruited between 1999 and 2005; 175 were randomly assigned to the MTX1 arm, and 177 were assigned to the MTX3 arm. Ninety-two percent of patients received protocol treatment. Median follow-up time is 3.7 years. Event-free survival (EFS) curves were superimposed with 2-year EFS rates (73.6% and 74.5% in the MTX1 and MTX3 arms, respectively; hazard ratio = 0.98; 91.76% CI, 0.69 to 1.38). Two-year overall survival rates were 90.1% and 94.9% in MTX1 and MTX3, respectively. Only two CNS relapses occurred (both in the MTX1 arm). Toxicity was assessed after 2,050 courses and included grade 4 hematologic toxicity after 79% and 64% of MTX1 and MTX3 courses, respectively (P < .0001); infection after 50% and 32% of courses, respectively (P < .0001); and grade 3 to 4 stomatitis after 21% and 6% of courses, respectively (P < .0001).
Conclusion: The results of the NHL-BFM90 study were reproduced in this large international trial. The methotrexate schedule of the NHL-BFM90 protocol including IT therapy can be safely replaced by a less toxic schedule of methotrexate 3 g/m2 in a 3-hour infusion without IT therapy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1200/JCO.2008.18.1487 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Hypoalbuminemia in children with acute lymphoblastic leukemia: relation to asparaginase therapy and impact on high dose methotrexate elimination.
Cancer Chemother Pharmacol
December 2024
Section of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescence Medicine, Aalborg University Hospital, Reberbansgade, 9000, Aalborg, Denmark.
Purpose: High-dose methotrexate (HDMTX) therapy is an important component in treatment regimens for acute lymphoblastic leukemia (ALL). Courses are associated with a risk of renal injury, delayed elimination, and increased systemic toxicity. Recently hypoalbuminemia has been recognized as yet another risk factor.
View Article and Find Full Text PDFIELSG30 phase 2 trial: intravenous and intrathecal CNS prophylaxis in primary testicular diffuse large B-cell lymphoma.
Blood Adv
March 2024
Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
Primary testicular diffuse large B-cell lymphoma (PTL) is characterized by high risk of contralateral testis and central nervous system (CNS) relapse. Chemoimmunotherapy with intrathecal (IT) CNS prophylaxis and contralateral testis irradiation eliminates contralateral recurrences and reduces CNS relapses. The IELSG30 phase 2 study investigated feasibility and activity of an intensified IT and IV CNS prophylaxis.
View Article and Find Full Text PDFEarly clinical indicators of acute kidney injury caused by administering high-dose methotrexate therapy to juvenile pigs.
Front Nephrol
September 2023
College of Nursing, Resonance, Memphis, TN, United States.
Introduction: Early identification of compromised renal clearance caused by high-dose methotrexate (HDMTX) is essential for initiating timely interventions that can reduce acute kidney injury and MTX-induced systemic toxicity.
Methods: We induced acute kidney injury (AKI) by infusing 42 juvenile pigs with 4 g/kg (80 g/m2) of MTX over 4 hours without high-volume alkalinizing hydration therapy. Concentrations of serum creatinine and MTX were measured at 15 time points up to 148 hours, with 10 samples collected during the first 24 hours after the start of the HDMTX infusion.
Primary central nervous system malignant lymphoma in a patient with rheumatoid arthritis receiving tocilizumab: illustrative case.
J Neurosurg Case Lessons
August 2022
4Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
Article Synopsis
- - Patients with rheumatoid arthritis (RA) have a higher risk of developing malignant lymphoma compared to the general population, but primary central nervous system lymphoma (PCNSL) in RA patients is very rare; this study presents the first documented case of PCNSL in a patient treated with the bDMARD tocilizumab.
- - A 70-year-old man with a history of RA treated with low-dose methotrexate and later tocilizumab developed gait issues, leading to brain imaging that revealed lesions; a biopsy confirmed the diagnosis of PCNSL, which was successfully managed with chemotherapy.
- - There are concerns that treatments like low-dose methotrexate and bDMARDs may increase cancer risk in RA
Objective: This study aims to investigate the characteristics and related high risk factors of second neoplasms after chemotherapy and radiotherapy in children with solid tumors.
Methods: The detailed clinical data of seven children with malignant solid tumors, who were treated in our department, were retrospectively analyzed, in order to summarize the clinical characteristics of the secondary onset of second neoplasms, and determined the risk factors related to the occurrence of second neoplasms.
Results: (1) Clinical characteristics: Among the seven children with malignant solid tumors, three children had rhabdomyosarcoma (3/132, 2.
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!