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CD371-positive pediatric B-cell acute lymphoblastic leukemia: propensity to lineage switch and slow early response to treatment
B. Buldini, E. Varotto, M. Maurer-Granofszky, G. Gaipa, A. Schumich, M. Brüggemann, E. Mejstrikova, G. Cazzaniga, O. Hrusak, M. Szczepanowski, P. Scarparo, M. Zimmermann, S. Strehl, D. Schinnerl, M. Zaliova, L. Karawajew, JP. Bourquin, T....
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't, Multicenter Study
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- MeSH
- Cell Lineage MeSH
- Child MeSH
- Immunophenotyping MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma * genetics mortality drug therapy pathology diagnosis therapy metabolism MeSH
- Child, Preschool MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Neoplasm, Residual * diagnosis MeSH
- Tetraspanins genetics metabolism MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
In the effort to improve immunophenotyping and minimal residual disease (MRD) assessment in acute lymphoblastic leukemia (ALL), the international Berlin-Frankfurt-Münster (iBFM) Flow Network introduced the myelomonocytic marker CD371 for a large prospective characterization with a long follow-up. In the present study, we aimed to investigate the clinical and biological features of CD371-positive (CD371pos) pediatric B-cell precursor ALL (BCP-ALL). From June 2014 to February 2017, 1812 pediatric patients with newly diagnosed BCP-ALLs enrolled in trial AIEOP-BFM ALL 2009 were evaluated as part of either a screening (n = 843, Italian centers) or validation cohort (n = 969, other iBFM centers). Laboratory assessment at diagnosis consisted of morphological, immunophenotypic, and genetic analysis. Response assessment relied on morphology, multiparametric flow cytometry (MFC), and polymerase chain reaction (PCR)-MRD. At diagnosis, 160 of 1812 (8.8%) BCP-ALLs were CD371pos. This correlated with older age, lower ETV6::RUNX1 frequency, immunophenotypic immaturity (all P < .001), and strong expression of CD34 and of CD45 (P < .05). During induction therapy, CD371pos BCP-ALLs showed a transient myelomonocytic switch (mm-SW: up to 65.4% of samples at day 15) and an inferior response to chemotherapy (slow early response, P < .001). However, the 5-year event-free survival was 88.3%. Among 420 patients from the validation cohort, 27 of 28 (96.4%) cases positive for DUX4-fusions were CD371pos. In conclusion, in the largest pediatric cohort, CD371 is the most sensitive marker of transient mm-SW, whose recognition is essential for proper MFC MRD assessment. CD371pos is associated to poor early treatment response, although a good outcome can be reached after MRD-based ALL-related therapies.
Department of Health Science and Public Health Catholic University of the Sacred Heart Rome Italy
Department of Pediatric Oncology Hematology Charité Universitätsmedizin Berlin Germany
Department of Pediatrics University Medical Center Schleswig Holstein Kiel Germany
Hannover Medical School Hannover Germany
Pediatrics IRCCS San Gerardo dei Tintori Monza Italy
School of Medicine and Surgery University of Milan Bicocca Monza Italy
References provided by Crossref.org
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