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Haematologica 2019 Volume 104(2):360-369
Chronic Lymphocytic Leukemia
Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia
Panagiotis Baliakas,1* Theodoros Moysiadis,2* Anastasia Hadzidimitriou,1,2 Aliki Xochelli,1,2 Sabine Jeromin,3 Andreas Agathangelidis,2 Mattias Mattsson,1 Lesley- Ann Sutton,1 Eva Minga,2 Lydia Scarfò,4 Davide Rossi,5 Zadie Davis,6 Neus Villamor,7 Helen Parker,8 Jana Kotaskova,9 Evangelia Stalika,2,10 Karla Plevova,9 Larry Mansouri,1 Diego Cortese,1 Alba Navarro,7 Julio Delgado,11 Marta Larrayoz,8 Emma Young,1 Achilles Anagnostopoulos,10 Karin E. Smedby,12 Gunnar Juliusson,13 Oonagh Sheehy,14 Mark Catherwood,14 Jonathan C. Strefford,8 Niki Stavroyianni,10 Chrysoula Belessi,15 Sarka Pospisilova,9 David Oscier,6 Gianluca Gaidano,16 Elias Campo,7,17 Claudia Haferlach,3 Paolo Ghia,4 Richard Rosenquist,18 Kostas Stamatopoulos;1,2 on behalf of The European Research Initiative on CLL (ERIC)
1Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden; 2Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece; 3MLL Munich Leukemia Laboratory, Munich, Germany; 4Division of Experimental Oncology, IRCCS Istituto Scientifico San Raffaele and Università Vita-Salute San Raffaele, Milan, Italy; 5Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; 6Department of Haematology, Royal Bournemouth Hospital, UK; 7Hemopathology Unit, Hospital Clinic, Barcelona, Spain; 8Cancer Genomics, Academic Unit of Cancer Sciences, Cancer Research UK Centre and Experimental Cancer Medicine Centre, Faculty of Medicine, University of Southampton, UK; 9Central European Institute of Technology, Masaryk University and University Hospital Brno, Czech Republic; 10Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece; 11Hematology Department, Hospital Clinic, Barcelona, Spain; 12Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden; 13Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Sweden; 14Department of Hemato-Oncology, Belfast City Hospital, UK; 15Hematology Department, Nikea General Hospital, Pireaus, Greece; 16Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy; 17Department of Pathology, University of Barcelona, Spain and 18Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
*PB and TM contributed equally to this work as first authors.
ABSTRACT
Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy vari- able genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indica- tors may differ between these two categories. Within Binet A M-CLL patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to- first-treatment and a treatment probability at five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet A U-CLL patients, besides TP53 abnormalities, del(11q) and/or SF3B1 mutations were associated with the shortest time-to-first- treatment (5- and 10-year treatment probability: 78% and 98%, respec- tively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage CLL patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmen- talized approaches based on immunogenetic features are necessary to refine and tailor prognostication in CLL.
Correspondence:
kostas.stamatopoulos@gmail.com
Received: April 12, 2018.
Accepted: September 25, 2018. Pre-published: September 27, 2018.
doi:10.3324/haematol.2018.195032
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/2/360
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