Redefining prognostication in chronic lymphocytic

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CLL is classified according to the somatic hypermutation status (SHM) of the immunoglobulin heavy variable (IGHV) genes, into mutated (M-CLL) and unmutated.

Redefining prognostication in chronic lymphocytic leukemia A novel multidisciplinary approach integrating disease heterogeneity Theodoros Moysiadis1*, Panagiotis Baliakas2*, Anastasia Hadzidimitriou1,2, Aliki Xochelli1,2, Mattias Mattsson2, Lesley-Ann Sutton2, Eva Minga1, Lydia Scarfò3,4, Davide Rossi5, Zadie Davis6, Andreas Agathangelidis1,3,4, Neus Villamor7, Helen Parker8, Jana Kotaskova9, Evangelia Stalika1,10, Karla Plevova9, Larry Mansouri2, Diego Cortese2, Alba Navarro Lopez7, Julio Delgado11, Marta Larrayoz8, Emma Young2, Achilles Anagnostopoulos10, Karin E Smedby12, Gunnar Juliusson13, Mark Catherwood15, Jonathan C. Strefford8, Niki Stavroyianni10, Chrysoula Belessi12, Sarka Pospisilova9, David Oscier6, Gianluca Gaidano5, Elias Campo7,16, Paolo Ghia3,4, Richard Rosenquist2, Kostas Stamatopoulos1,2; on behalf of The European Research Initiative on CLL (ERIC). 1. Institute of Applied Biosciences, CERTH, Thessaloniki, Greece, 2. Department of Immunology, Genetics and Pathology, Uppsala University, Sweden, 3. Division of experimental Oncology and Department of Onco-Hematology, Istituto Scientfico San Raffaele e Fondazione Centro San Raffaele, Milan, Italy, 4. Università Vita-Salute San Raffaele, Milan, Italy, 5. Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy, 6. Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK, 7. Hemopathology Unit, Hospital Clinic, Barcelona, Spain, 8. Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK, 9. Central European Institute of Technology, Masaryk University and University Hospital Brno, Czech Republic, 10. Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece, 11. Hematology Department, Hospital Clinic, Barcelona, Spain, 12. Hematology Department, Nikea General Hospital, Pireaus, Greece, 13. Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden, 14. Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden, 15. Department of Hemato-Oncology, Belfast City Hospital, Belfast, United Kingdom, 16. Department of Pathology, University of Barcelona, Spain.

Why focus on chronic lymphocytic leukemia (CLL)

Table 1: Univariable and multivariable analysis for TTFT within the M- and U-CLL group and internal validation results.

The most common adult leukemia in the West (11000 diagnoses/year in Europe). Remarkable clinical heterogeneity: urgent need for robust prognostication. Chronic disease: rendering personalized medicine an ideal objective.

Research Objectives of CLLassify Refined classification for CLL patients.

Parameters Male CD38 expression +12 TP53abs GI:97-97.99% Subset #2

Application of a novel class of statistical predictive models. Development of a package in the statistical programming language ‘R’.

The standard way to prognostication in CLL A large number of prognostic biomarkers is available. Identification of the so called “independent predictors”, usually via Cox regression analysis.

Parameters Male +12 del(11q) TP53abs SF3B1 mutations

Univariable analysis (n=1228) HR p-value 1.35 2.01 2.42 3.34 1.57 3.38

0.013