Prognostic Relevance of CD200/Btla Deletions in Pediatric Precursor-B Cell Acute Lymphoblastic Leukemia Treated According to the EORTC-CLG 58951 Protocol

• Published in: Blood 2014-12, Vol.124 (21), p.2394-2394
• Main Authors: Ghazavi, Farzaneh, Lammens, Tim, Clappier, Emmanuelle, Suciu, Stefan, Caye, Aurélie, Zegrari, Samira, Bakkus, Marleen, Grardel, Nathalie, Benoit, Yves, Bertrand, Yves, Minckes, Odile, Costa, Vitor, Ferster, Alina, Mazingue, Françoise, Plat, Geneviève, Plouvier, Emmanuel, Poirée, Marilyne, Uyttebroeck, Anne, Van der Werff Ten Bosch, Jutte, Helsmoortel, Hetty, Meul, Magali, Van Roy, Nadine, Philippé, Jan, Speleman, Frank, Cavé, Hélène, Van Vlierberghe, Pieter, De Moerloose, Barbara
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V124.21.2394.2394

Introduction: Despite the use of current risk classification in children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), a substantial proportion of so-called standard risk patients will experience a hematological relapse. Detection of DNA copy number abnormalities in BCP-ALLs has revealed additional genetic alterations, some of which are associated with outcome and may be included in future stratification strategies. Materials and methods: Using array-comparative genomic hybridization in a selected cohort of 70 intermediate risk pediatric BCP-ALLs, we characterized a recurrent RAG-mediated deletion of the CD200 and BTLA genes in 10% of patients. A breakpoint-specific PCR assay was designed and used to screen an independent non-selected cohort of 1154 genetically well-characterized BCP-ALLs uniformly treated according to the BFM-based EORTC-58951 protocol. Results: CD200/BTLA deletions were identified in 56 patients of the non-selected cohort (4.8%). Survival analysis revealed that CD200/BTLA deletions are associated with an inferior 8-year event free survival (EFS) of 70.2% ± 1.2% for patients with the deletions versus 83.5% ± 6.4% for non-deleted cases (HR 2.02; 95% CI 1.23-3.32; p=0.005) in the complete cohort of 1154 BCP-ALL patients. We observed a strong association between CD200/BTLA deletions and ETV6-RUNX1 positive leukemias (Table 1). The presence of ETV6-RUNX1 is a good prognostic marker in BCP-ALL and CD200/BTLA deletions did not affect prognosis within this genetic subtype. However and most notably, CD200/BTLA deletions were also identified in patients without any known genetic lesion, who are classified as having an intermediate outcome and belong to the intermediate-risk genetic group (defined in Table 1). Within this genetic group an inferior 8-year EFS rate of 33.3% (95% CI 7.8%-62.3%) was observed for patients with the deletions versus 76.2% (95% CI 71.0%-80.6%) for non-deleted cases (HR 4.00; 99% CI 1.34-11.93; p