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Four Additional Doses of PEG-L-Asparaginase During the Consolidation Phase in the AIEOP-BFM ALL 2009 Protocol Do Not Improve Outcome and Increase Toxicity in High-Risk ALL: Results of a Randomized Study
V. Conter, MG. Valsecchi, G. Cario, M. Zimmermann, A. Attarbaschi, J. Stary, F. Niggli, L. Dalla Pozza, S. Elitzur, D. Silvestri, F. Locatelli, A. Möricke, G. Engstler, P. Smisek, N. Bodmer, D. Barbaric, S. Izraeli, C. Rizzari, J. Boos, B....
Language English Country United States
Document type Clinical Trial Protocol, Journal Article
NLK
Free Medical Journals
from 2004 to 1 year ago
Open Access Digital Library
from 1999-01-01
PubMed
38096462
DOI
10.1200/jco.23.01388
Knihovny.cz E-resources
- MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma * MeSH
- Asparaginase * MeSH
- Infant MeSH
- Humans MeSH
- Neoplasm Recurrence, Local drug therapy MeSH
- Polyethylene Glycols MeSH
- Prednisone adverse effects MeSH
- Disease-Free Survival MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects MeSH
- Randomized Controlled Trials as Topic MeSH
- Recurrence MeSH
- Treatment Outcome MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial Protocol MeSH
PURPOSE: The AIEOP-BFM ALL 2009 protocol included, at the end of the induction phase, a randomized study of patients with high-risk (HR) ALL to investigate if an intensive exposure to pegylated L-asparaginase (PEG-ASNASE, 2,500 IU/sqm once a week × 4) on top of BFM consolidation phase IB allowed us to decrease minimal residual disease (MRD) and improve outcome. PATIENTS AND METHODS: A total of 1,097 patients presented, from June 2010 to February 2017, with one or more of the following HR criteria: KMT2A::AFF1 rearrangement, hypodiploidy, prednisone poor response, poor bone marrow response at day 15 (Flow MRD ≥10%), or no complete remission (CR) at the end of induction. Of them, 809 (85.1%) were randomly assigned to receive (404) or not receive (405) four weekly doses of PEG-ASNASE. RESULTS: By intention to treat (ITT) analysis, there was no significant difference in the proportion of patients with polimerase chain reaction MRD ≥5 × 10-4 at the end of phase IB in the experimental versus control arm (13.9% v 17.0%, P = .25). The 5-year event-free survival (median follow-up 6.3 years) by ITT in the experimental and control arms was 70.4% (2.3) versus 75.0% (2.2; P = .18), and the 5-year overall survival was 81.5% (2.0) versus 84.0% (1.9; P = .25), respectively. The corresponding 5-year cumulative incidence of death in CR was 9.5% (1.5) versus 5.7% (1.2; P = .08), and that of relapse was 17.7% (1.9) versus 17.2% (1.9), respectively (P = .94). Adverse reactions in phase IB occurred in 22.2% and 8.9% of patients in the experimental and control arm, respectively (P < .001). CONCLUSION: Additional PEG-ASNASE in phase IB did not translate into a benefit for decreasing relapse incidence but was associated with higher toxicity. Further improvements with conventional chemotherapy might be difficult in the context of intensive treatment protocols.
Biostatistics and Clinical Epidemiology Fondazione IRCCS San Gerardo dei Tintori Monza Italy
Department of Paediatric Hematology and Oncology University Hospital Muenster Muenster Germany
Department of Pediatric Hematology Oncology Hannover Medical School Hannover Germany
Department of Pediatrics Jena University Hospital Jena Germany
Kids Cancer Centre Sydney Children's Hospital Randwick NSW Australia
Pediatrics Fondazione IRCCS San Gerardo dei Tintori Monza Italy
School of Medicine and Surgery University of Milano Bicocca Milan Italy
St Anna Children's Cancer Research Institute Vienna Austria
Tettamanti Center Fondazione IRCCS San Gerardo dei Tintori Monza Italy
The Cancer Centre for Children The Children's Hospital at Westmead Sydney NSW Australia
University Children Hospital Zurich Department of Oncology Zurich Switzerland
References provided by Crossref.org
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