Validation of the United Kingdom copy-number alteration classifier in 3239 children with B-cell precursor ALL.

Autor:	Hamadeh L; Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom., Enshaei A; Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom., Schwab C; Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom., Alonso CN; Hematology-Oncology Department, Hospital de Pediatría 'Prof. Dr. J. P. Garrahan,' Buenos Aires, Argentina., Attarbaschi A; Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria., Barbany G; Department of Molecular Medicine and Surgery, Clinical Genetics Section, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., den Boer ML; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Boer JM; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Braun M; Department of Pathology, Medical University of Lodz, Lodz, Poland., Dalla Pozza L; Cancer Center for Children, Sydney Childrens Hospital Network, Westmead, NSW, Australia., Elitzur S; Pediatric Hematology Oncology, Schneider Children's Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Emerenciano M; Division of Clinical Research, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, Brazil., Fechina L; Regional Children's Hospital 1, Ekaterinburg, Russia.; Research Institute of Medical Cell Technologies, Ekaterinburg, Russia., Felice MS; Hematology-Oncology Department, Hospital de Pediatría 'Prof. Dr. J. P. Garrahan,' Buenos Aires, Argentina., Fronkova E; Childhood Leukaemia Investigation, Prague, Czech Republic.; Department of Paediatric Haematology/Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic., Haltrich I; 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary., Heyman MM; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden., Horibe K; Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan., Imamura T; Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan., Jeison M; Cancer Cytogenetic Laboratory, Schneider Children's Medical Center of Israel, Petah Tikva, Israel., Kovács G; 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary., Kuiper RP; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Mlynarski W; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Nebral K; Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria., Ivanov Öfverholm I; Department of Molecular Medicine and Surgery, Clinical Genetics Section, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Pastorczak A; Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland., Pieters R; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Dutch Childhood Oncology Group, Utrecht, The Netherlands., Piko H; 1st Department of Medicine, Semmelweis University, Budapest, Hungary., Pombo-de-Oliveira MS; Pediatric Haematology-Oncology Program, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, Brazil., Rubio P; Hematology-Oncology Department, Hospital de Pediatría 'Prof. Dr. J. P. Garrahan,' Buenos Aires, Argentina., Strehl S; Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria., Stary J; Department of Paediatric Haematology/Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic., Sutton R; Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia; and., Trka J; Childhood Leukaemia Investigation, Prague, Czech Republic.; Department of Paediatric Haematology/Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic., Tsaur G; Regional Children's Hospital 1, Ekaterinburg, Russia.; Research Institute of Medical Cell Technologies, Ekaterinburg, Russia., Venn N; Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia; and., Vora A; Department of Haematology, Great Ormond Street Hospital, London, United Kingdom., Yano M; Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan., Harrison CJ; Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom., Moorman AV; Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2019 Jan 22; Vol. 3 (2), pp. 148-157.
DOI:	10.1182/bloodadvances.2018025718
Abstrakt:	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. (© 2019 by The American Society of Hematology.)
Databáze:	MEDLINE
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