Long-Term Results of a Randomized Trial on Extended Use of High Dose l-Asparaginase for Standard Risk Childhood Acute Lymphoblastic Leukemia
- 1 October 2005
- journal article
- clinical trial
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 23 (28), 7161-7167
- https://doi.org/10.1200/jco.2005.11.411
Abstract
Purpose: Between September 1991 and May 1997, within the International Berlin-Frankfurt-Muenster Study Group (I-BFM-SG), a randomized study was performed aimed at assessing the efficacy of prolonged use of high-dose l-asparaginase (HD-l-ASP) during continuation therapy in children with standard risk (SR) acute lymphoblastic leukemia (ALL), treated with a reduced BFM-type chemotherapy. Patients and Methods: The Italian, Dutch, and Hungarian groups participated in this study denominated IDH-ALL-91, and 494 children were enrolled. Treatment consisted of a BFM-type modified backbone with omission of the IB part in induction and elimination of two doses of anthracyclines during reinduction in both arms at the beginning of continuation therapy. Patients were randomly assigned to receive (YES-ASP) or not (NO-ASP) 20 weekly HD-l-ASP (25,000 IU/m2). Results: The event-free-survival and overall survival probabilities at 10 years for the entire group were 82.5% (1.8) and 90.3% (1.3), respectively. Of the 490 patients eligible for random assignment, 355 (72.4%) were randomly assigned (178 YES-ASP and 177 NO-ASP). After a median follow-up of 9 years, the probability of disease-free survival at 10 years was 87.5% (SE, 2.5) for YES-ASP arm versus 78.7% (SE, 3.3) for NO-ASP arm (P = .03). In multivariate analysis, NO-ASP arm (P = .03), male sex (P = .004), and age older than 10 years (P = .0003) had a significantly adverse impact on outcome. Conclusion: In this subset of patients, selected with criteria not including monitoring of minimal residual disease, application of extended HD-l-ASP may improve prognosis, compensating reduced leukemia control that results from adoption of a reduced-intensity BFM-backbone for treatment of children with SR ALL.Keywords
This publication has 19 references indexed in Scilit:
- Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research HospitalBlood, 2004
- Long-term results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) Acute Lymphoblastic Leukemia Studies, 1982–1995Leukemia, 2000
- Long-term follow-up of Dutch Childhood Leukemia Study Group (DCLSG) protocols for children with acute lymphoblastic leukemia, 1984–1991Leukemia, 2000
- Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981–1995)Leukemia, 2000
- Long-term results of Total Therapy studies 11, 12 and 13A for childhood acute lymphoblastic leukemia at St Jude Children's Research HospitalLeukemia, 2000
- Co-operative study group for childhood acute lymphoblastic leukemia (COALL): long-term follow-up of trials 82, 85, 89 and 92Leukemia, 2000
- Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983–1995Leukemia, 2000
- Comparative pharmacokinetic studies of three asparaginase preparations.Journal of Clinical Oncology, 1993
- Four-Agent Induction and Intensive Asparaginase Therapy for Treatment of Childhood Acute Lymphoblastic LeukemiaNew England Journal of Medicine, 1986
- E. coli L-asparaginase in the treatment of leukemia and solid tumors in 131 childrenCancer, 1970