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Chronic Lymphocytic Leukemia
Chromosome banding analysis and genomic microarrays are both useful but not equiva- lent methods for genomic complexity risk stratification in chronic lymphocytic leukemia patients
Silvia Ramos-Campoy,1,2* Anna Puiggros,1,2* Sílvia Beà,3 Sandrine Bougeon,4 María José Larráyoz,5 Dolors Costa,3 Helen Parker,6 Gian Matteo Rigolin,7 Margarita Ortega,8 María Laura Blanco,9 Rosa Collado,10 Rocío Salgado,11 Tycho Baumann,3 Eva Gimeno,1,12 Carolina Moreno,9 Francesc Bosch,8 Xavier Calvo,1,2 María José Calasanz,5 Antonio Cuneo,7 Jonathan C. Strefford,6 Florence Nguyen-Khac,13 David Oscier,14 Claudia Haferlach,15 Jacqueline Schoumans4 and Blanca Espinet1,2
1Molecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar, Barcelona, Spain; 2Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain; 3Hematopathology Unit, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERONC, Barcelona, Spain; 4Oncogenomic Laboratory, Hematology Service, Lausanne University Hospital, Lausanne, Switzerland; 5Cytogenetics and Hematological Genetics Services, Department of Genetics, University of Navarra, Pamplona, Spain; 6Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; 7Hematology Section, St. Anna University Hospital, Ferrara, Italy; 8Department of Hematology, University Hospital Vall d'Hebron, Barcelona, Spain; 9Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 10Department of Hematology, Consorcio Hospital General Universitario, Valencia, Spain; 11Cytogenetics Laboratory, Hematology Department, Fundación Jiménez Díaz, Madrid, Spain; 12Applied Clinical Research in Hematological Malignances, Cancer Research Program, IMIM-Hospital del Mar, Barcelona, Spain; 13Hematology Department and Sorbonne Université, Hôpital Pitié-Salpêtrière, APHP, INSERM U1138, Paris, France; 14Department of Molecular Pathology, Royal Bournemouth Hospital, Bournemouth, UK and 15MLL Munich Leukemia Laboratory, Munich, Germany
*SR-C and AP contributed equally as co-first authors.
ABSTRACT
Genome complexity has been associated with poor outcome in patients with chronic lymphocytic leukemia (CLL). Previous co- operative studies established five abnormalities as the cut-off that best predicts an adverse evolution by chromosome banding analy- sis (CBA) and genomic microarrays (GM). However, data comparing risk stratification by both methods are scarce. Herein, we assessed a cohort of 340 untreated CLL patients highly enriched in cases with com- plex karyotype (CK) (46.5%) with parallel CBA and GM studies. Abnormalities found by both techniques were compared. Prognostic stratification in three risk groups based on genomic complexity (0-2, 3- 4 and ≥5 abnormalities) was also analyzed. No significant differences in the percentage of patients in each group were detected, but only a mod- erate agreement was observed between methods when focusing on individual cases (κ=0.507; P<0.001). Discordant classification was obtained in 100 patients (29.4%), including 3% classified in opposite risk groups. Most discrepancies were technique-dependent and no greater correlation in the number of abnormalities was achieved when different filtering strategies were applied for GM. Nonetheless, both methods showed a similar concordance index for prediction of time to first treatment (TTFT) (CBA: 0.67 vs. GM: 0.65) and overall survival (CBA: 0.55 vs. GM: 0.57). High complexity maintained its significance in the multivariate analysis for TTFT including TP53 and IGHV status when defined by CBA (hazard ratio [HR] 3.23; P<0.001) and GM (HR
Ferrata Storti Foundation
Haematologica 2022 Volume 107(3):593-603
Correspondence:
BLANCA ESPINET
bespinet@parcdesalutmar.cat
ANNA PUIGGROS
apuiggros@imim.es
Received: November 27, 2020. Accepted: February 26, 2021. Pre-published: March 11, 2021.
https://doi.org/10.3324/haematol.2020.274456 ©2022 Ferrata Storti Foundation
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