Genetic abnormalities provide vital diagnostic and prognostic information in pediatric acute lymphoblastic leukemia (ALL) and are increasingly used to assign patients to risk groups. We recently proposed a novel classifier based on the copy-number alteration (CNA) profile of the 8 most commonly deleted genes in B-cell precursor ALL. This classifier defined 3 CNA subgroups in consecutive UK trials and was able to discriminate patients with intermediate-risk cytogenetics. In this study, we sought to validate the United Kingdom ALL (UKALL)-CNA classifier and reevaluate the interaction with cytogenetic risk groups using individual patient data from 3239 cases collected from 12 groups within the International BFM Study Group. The classifier was validated and defined 3 risk groups with distinct event-free survival (EFS) rates: good (88%), intermediate (76%), and poor (68%) (P < .001). There was no evidence of heterogeneity, even within trials that used minimal residual disease to guide therapy. By integrating CNA and cytogenetic data, we replicated our original key observation that patients with intermediate-risk cytogenetics can be stratified into 2 prognostic subgroups. Group A had an EFS rate of 86% (similar to patients with good-risk cytogenetics), while group B patients had a significantly inferior rate (73%, P < .001). Finally, we revised the overall genetic classification by defining 4 risk groups with distinct EFS rates: very good (91%), good (81%), intermediate (73%), and poor (54%), P < .001. In conclusion, the UKALL-CNA classifier is a robust prognostic tool that can be deployed in different trial settings and used to refine established cytogenetic risk groups.

1st Department of Medicine Semmelweis University Budapest Hungary

2nd Department of Paediatrics Semmelweis University Budapest Hungary

Cancer Center for Children Sydney Childrens Hospital Network Westmead NSW Australia

Cancer Cytogenetic Laboratory Schneider Children's Medical Center of Israel Petah Tikva Israel

Childhood Leukaemia Investigation Prague Czech Republic

Children's Cancer Institute Lowy Cancer Research Centre University of New South Wales Sydney NSW Australia; and

Children's Cancer Research Institute St Anna Kinderkrebsforschung Vienna Austria

Clinical Research Center National Hospital Organization Nagoya Medical Center Nagoya Japan

Department of Haematology Great Ormond Street Hospital London United Kingdom

Department of Molecular Medicine and Surgery Clinical Genetics Section Center for Molecular Medicine Karolinska Institutet Stockholm Sweden

Department of Paediatric Haematology Oncology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Department of Pathology Medical University of Lodz Lodz Poland

Department of Pediatric Hematology and Oncology St Anna Children's Hospital Medical University of Vienna Vienna Austria

Department of Pediatrics Kyoto Prefectural University of Medicine Kyoto Japan

Department of Pediatrics Oncology and Hematology Medical University of Lodz Lodz Poland

Department of Women's and Children's Health Karolinska Institutet Stockholm Sweden

Division of Clinical Research Research Centre Instituto Nacional de Câncer Rio de Janeiro Brazil

Dutch Childhood Oncology Group Utrecht The Netherlands

Hematology Oncology Department Hospital de Pediatría Prof Dr J P Garrahan Buenos Aires Argentina

Pediatric Haematology Oncology Program Research Centre Instituto Nacional de Câncer Rio de Janeiro Brazil

Pediatric Hematology Oncology Schneider Children's Medical Center Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands

Regional Children's Hospital 1 Ekaterinburg Russia

Research Institute of Medical Cell Technologies Ekaterinburg Russia

Wolfson Childhood Cancer Research Centre Northern Institute for Cancer Research Newcastle University Newcastle United Kingdom

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The Clinical Utility of Optical Genome Mapping for the Assessment of Genomic Aberrations in Acute Lymphoblastic Leukemia

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