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Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol
J. Stutterheim, IM. van der Sluis, P. de Lorenzo, J. Alten, P. Ancliffe, A. Attarbaschi, B. Brethon, A. Biondi, M. Campbell, G. Cazzaniga, G. Escherich, A. Ferster, RS. Kotecha, B. Lausen, CK. Li, L. Lo Nigro, F. Locatelli, R. Marschalek, C....
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 2004 to 1 year ago
Open Access Digital Library
from 1999-01-01
PubMed
33405950
DOI
10.1200/jco.20.02333
Knihovny.cz E-resources
- MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma complications MeSH
- Humans MeSH
- Prognosis MeSH
- Neoplasm, Residual etiology physiopathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
PURPOSE: Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with KMT2A-rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide). MATERIALS AND METHODS: MRD was measured in 249 infants by DNA-based polymerase chain reaction of rearranged KMT2A, immunoglobulin, and/or T-cell receptor genes, at the end of induction (EOI) and end of consolidation (EOC). MRD results were classified as negative, intermediate (< 5 × 10-4), and high (≥ 5 × 10-4). RESULTS: EOI MRD levels predicted outcome with 6-year disease-free survival (DFS) of 60.2% (95% CI, 43.2 to 73.6), 45.0% (95% CI, 28.3 to 53.1), and 33.8% (95% CI, 23.8 to 44.1) for infants with negative, intermediate, and high EOI MRD levels, respectively (P = .0039). EOC MRD levels were also predictive of outcome, with 6-year DFS of 68.2% (95% CI, 55.2 to 78.1), 40.1% (95% CI, 28.1 to 51.9), and 11.9% (95% CI, 2.6 to 29.1) for infants with negative, intermediate, and high EOC MRD levels, respectively (P < .0001). Analysis of EOI MRD according to the type of consolidation treatment showed that infants treated with lymphoid-style consolidation had 6-year DFS of 78.2% (95% CI, 51.4 to 91.3), 47.2% (95% CI, 33.0 to 60.1), and 23.2% (95% CI, 12.1 to 36.4) for negative, intermediate, and high MRD levels, respectively (P < .0001), while for myeloid-style-treated patients the corresponding figures were 45.0% (95% CI, 23.9 to 64.1), 41.3% (95% CI, 23.2 to 58.5), and 45.9% (95% CI, 29.4 to 60.9). CONCLUSION: This study provides support for the idea that induction therapy selects patients for subsequent therapy; infants with high EOI MRD may benefit from AML-like consolidation (DFS 45.9% v 23.2%), whereas patients with low EOI MRD may benefit from ALL-like consolidation (DFS 78.2% v 45.0%). Patients with positive EOC MRD had dismal outcomes. These findings will be used for treatment interventions in the next Interfant protocol.
Berlin Frankfurt Miünster Group Germany Kiel Germany
Center of Bioinformatics Biostatistics and Bioimaging University of Milano Bicocca Monza Italy
Chilean National Pediatric Oncology Group Santiago Chile
Czech Working Group for Pediatric Hematology Prague Czech Republic
DCAL Institute of Pharmaceutical Biology Goethe University Frankfurt am Main Germany
Department of Immunology Erasmus University Medical Center Rotterdam the Netherlands
Department of Pediatric Hematology University Robert Debre Hospital APHP Paris France
Department of Pediatrics UKSH Kiel Germany
Dutch Childhood Oncology Group Utrecht the Netherlands
European Organisation for Research and Treatment of Cancer Children Leukemia Group Brussels Belgium
German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia Hamburg Germany
Polish Pediatric Leukemia Lymphoma Study Group Zabrze Medical University of Silesia Katowice Poland
Princess Máxima Center for Pediatric Oncology Utrecht the Netherlands
St Anna Children's Hospital Medical University of Vienna Vienna Austria
Telethon Kids Cancer Centre Telethon Kids Institute University of Western Australia Perth Australia
United Kingdom Children Cancer Study Group London United Kingdom
References provided by Crossref.org
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