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Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY
T. Chatzikonstantinou, L. Scarfò, G. Karakatsoulis, E. Minga, D. Chamou, G. Iacoboni, J. Kotaskova, C. Demosthenous, L. Smolej, S. Mulligan, M. Alcoceba, S. Al-Shemari, T. Aurran-Schleinitz, F. Bacchiarri, M. Bellido, F. Bijou, A. Calleja, A....
Status not-indexed Language English Country England, Great Britain
Document type Journal Article
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- Publication type
- Journal Article MeSH
BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work. METHODS: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022. FINDINGS: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79-4.91; p < 0.001). STs were more frequent in males and patients with unmutated immunoglobulin heavy variable genes (OR = 1.77; 95% CI = 1.49-2.11; p < 0.001/OR = 1.89; 95% CI = 1.6-2.24; p < 0.001).CLL-directed treatment was associated with non-melanoma skin and prostate cancers (OR = 1.8; 95% CI = 1.36-2.41; p < 0.001/OR = 2.11; 95% CI = 1.12-3.97; p = 0.021). In contrast, breast cancers were more frequent in untreated patients (OR = 0.17; 95% CI = 0.08-0.33; p < 0.001).Patients with CLL and an OM had inferior overall survival (OS) than those without. AML and MDS conferred the worst OS (p < 0.001). INTERPRETATION: OMs in CLL impact on OS. Treatment for CLL increased the risk for AML/MDS, prostate cancer, and NMSC. FCR was associated with increased risk for AML/MDS. FUNDING: AbbVie, and EU/EFPIAInnovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026.
Antalya Training and Research Hospital Antalya Turkey
Central European Institute of Technology Masaryk University Brno Czech Republic
Clinic for Hematology University Clinical Center of Serbia Belgrade Serbia
Clinical Haematology Belfast City Hospital Belfast United Kingdom
Department of Clinical Hematology ICO Hospital Duran i Reynals IDIBELL Barcelona Spain
Department of Haematology Athens Medical Center Psychikon Branch Athens Greece
Department of Haematology Royal Bournemouth Hospital Bournemouth United Kingdom
Department of Haematology University Hospital of Salamanca Salamanca Spain
Department of Haematology University Hospital Vall d'Hebron Autonomous University Barcelona Spain
Department of Haematooncology University Hospital Ostrava Ostrava Czech Republic
Department of Hemato Oncology Institut Paoli Calmettes Marseille France
Department of Hematology and Cell Therapy Estaing University Hospital Clermont Ferrand France
Department of Hematology Centre Hospitalier Le Mans Le Mans France
Department of Hematology Hospital del Mar Barcelona Spain
Department of Hematology Hospital Universitario de Burgos Burgos Spain
Department of Hematology Oncology and Chemotherapy S P Botkin's City Hospital Moscow Russia
Department of Hematology Shamir Medical Center Zerifin Israel
Department of Hematology University Hospital Dubrava Zagreb Croatia
Department of Hematology University Hospital Marqués de Valdecilla Santander Spain
Department of Internal Medicine Albert Schweitzer Hospital Dordrecht the Netherlands
Department of Mathematics University of Ioannina Ioannina Greece
Department of Medicine Pamela Youde Nethersole Eastern Hospital Chai Wan Hong Kong China
Department of Medicine School of Clinical Medicine The University of Hong Kong Hong Kong China
Department of Molecular Hematology National Medical Research Center for Hematology Moscow Russia
Dept Hematooncology and Bone Marrow Transplantation Medical University in Lublin Lublin Poland
Division of Hematology Dokuz Eylul University Izmir Turkey
Division of Hematology University of Siena Siena Italy
Experimental Hematooncology Department Medical University of Lublin Lublin Poland
Faculty of Medicine Clinical Centre of Vojvodina University of Novi Sad Novi Sad Serbia
Faculty of Medicine Department of Medicine Kuwait University Kuwait City Kuwait
Faculty of Medicine University of Belgrade Belgrade Serbia
Fundacion Jimenez Diaz University Hospital Health Research Institute IIS FJD Madrid Spain
Gazi University Medical Faculty Ankara Turkey
Haematology Department Hospital Universitario de La Princesa Madrid Spain
Haematology University of Athens Laikon General Hospital Athens Greece
Hematology and Clinical Immunology Unit Department of Medicine University of Padova Padova Italy
Hematology Bnai Zion Medical Center Haifa Israel
Hematology Clinic ASUFC Udine Italy
Hematology Department and HCT Unit G Papanicolaou Hospital Thessaloniki Greece
Hematology Department Colentina Clinical Hospital Bucharest Romania
Hematology Department Hospital Universitario 12 de Octubre Madrid Spain
Hematology Department Infanta Leonor University Hospital Madrid Spain
Hematology Department Ramón y Cajal University Hospital Madrid Spain
Hematology Department St John's Cancer Center Lublin Poland
Hematology Unit 1st Dept of Internal Medicine AUTH AHEPA Hospital Thessaloniki Greece
Hematology Unit Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan Milan Italy
Hematopathology Laboratory Hamad Medical Corporation Doha Qatar
Hospital Costa del Sol Málaga Spain
Hospital de Clinicas Montevideo Uruguay
Hospital Italiano La Plata Buenos Aires Argentina
Hull York Medical School Hull United Kingdom
Institut Bergonié Bordeaux France
Institute of Applied Biosciences Centre for Research and Technology Hellas Thessaloniki Greece
Internal Medicine Department Universidade Federal do Espírito Santo Vila Velha ES Brazil
Laboratory Oncology Unit Dr B R A IRCH All India Institute of Medical Sciences New Delhi India
Oncology Center Mansoura University Mansoura Egypt
Pathology Faculty of Medicine University of Augsburg Stenglinstrasse 2 Augsburg 86156 Germany
Royal North Shore Hospital Sydney NSW Australia
Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
Section of Hematology Department of Clinical and Experimental Medicine University of Pisa Pisa Italy
Service d'Hématologie Oncologie Centre Hospitalier de Versailles Le Chesnay France
St Anna University Hospital Ferrara Italy
Università Vita Salute San Raffaele and IRCCS Ospedale San Raffaele Milan Italy
References provided by Crossref.org
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- $a Chatzikonstantinou, Thomas $u Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece
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- $a Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY / $c T. Chatzikonstantinou, L. Scarfò, G. Karakatsoulis, E. Minga, D. Chamou, G. Iacoboni, J. Kotaskova, C. Demosthenous, L. Smolej, S. Mulligan, M. Alcoceba, S. Al-Shemari, T. Aurran-Schleinitz, F. Bacchiarri, M. Bellido, F. Bijou, A. Calleja, A. Medina, MA. Khan, R. Cassin, S. Chatzileontiadou, R. Collado, A. Christian, Z. Davis, M. Dimou, D. Donaldson, GD. Santos, B. Dreta, M. Efstathopoulou, S. El-Ashwah, A. Enrico, A. Fresa, S. Galimberti, A. Galitzia, R. García-Serra, E. Gimeno, I. González-Gascón-Y-Marín, A. Gozzetti, V. Guarente, R. Guieze, A. Gogia, R. Gupta, S. Harrop, E. Hatzimichael, Y. Herishanu, JÁ. Hernández-Rivas, L. Inchiappa, O. Jaksic, S. Janssen, E. Kalicińska, L. Kamel, V. Karakus, AP. Kater, B. Kho, M. Kislova, E. Konstantinou, M. Koren-Michowitz, I. Kotsianidis, RJ. Kreitman, J. Labrador, D. Lad, MD. Levin, I. Levy, T. Longval, A. Lopez-Garcia, J. Marquet, L. Martin-Rodríguez, M. Maynadié, S. Maslejova, C. Mayor-Bastida, B. Mihaljevic, I. Milosevic, F. Miras, R. Moia, M. Morawska, R. Murru, UK. Nath, A. Navarro-Bailón, AC. Oliveira, J. Olivieri, D. Oscier, I. Panovska-Stavridis, M. Papaioannou, T. Papajík, Z. Kubova, P. Phumphukhieo, C. Pierie, A. Puiggros, L. Rani, G. Reda, GM. Rigolin, R. Ruchlemer, M. Daniel de Deus Santos, M. Schipani, A. Schiwitza, Y. Shen, M. Simkovic, S. Smirnova, DS. Abdelrahman Soliman, M. Spacek, T. Tadmor, K. Tomic, E. Tse, T. Vassilakopoulos, A. Visentin, C. Vitale, J. von Tresckow, G. Vrachiolias, V. Vukovic, R. Walewska, E. Wasik-Szczepanek, Z. Xu, M. Yagci, L. Yañez, M. Yassin, J. Zuchnicka, M. Angelopoulou, D. Antic, B. Biderman, M. Catherwood, R. Claus, M. Coscia, A. Cuneo, F. Demirkan, B. Espinet, G. Gaidano, OB. Kalashnikova, L. Laurenti, E. Nikitin, GA. Pangalis, P. Panagiotidis, VM. Popov, S. Pospisilova, P. Sportoletti, N. Stavroyianni, C. Tam, L. Trentin, A. Chatzidimitriou, F. Bosch, M. Doubek, P. Ghia, K. Stamatopoulos
- 520 9_
- $a BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work. METHODS: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022. FINDINGS: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79-4.91; p < 0.001). STs were more frequent in males and patients with unmutated immunoglobulin heavy variable genes (OR = 1.77; 95% CI = 1.49-2.11; p < 0.001/OR = 1.89; 95% CI = 1.6-2.24; p < 0.001).CLL-directed treatment was associated with non-melanoma skin and prostate cancers (OR = 1.8; 95% CI = 1.36-2.41; p < 0.001/OR = 2.11; 95% CI = 1.12-3.97; p = 0.021). In contrast, breast cancers were more frequent in untreated patients (OR = 0.17; 95% CI = 0.08-0.33; p < 0.001).Patients with CLL and an OM had inferior overall survival (OS) than those without. AML and MDS conferred the worst OS (p < 0.001). INTERPRETATION: OMs in CLL impact on OS. Treatment for CLL increased the risk for AML/MDS, prostate cancer, and NMSC. FCR was associated with increased risk for AML/MDS. FUNDING: AbbVie, and EU/EFPIAInnovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026.
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- 700 1_
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- $a Vassilakopoulos, Theodoros $u Haematology, University of Athens, Laikon General Hospital, Athens, Greece
- 700 1_
- $a Visentin, Andrea $u Hematology and Clinical Immunology Unit, Department of Medicine, University of Padova, Padova, Italy
- 700 1_
- $a Vitale, Candida $u Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino and Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy
- 700 1_
- $a von Tresckow, Julia $u Clinic for Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- 700 1_
- $a Vrachiolias, George $u Department of Hematology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece
- 700 1_
- $a Vukovic, Vojin $u Clinic for Hematology, University Clinical Center of Serbia, Belgrade, Serbia $u Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- 700 1_
- $a Walewska, Renata $u Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom
- 700 1_
- $a Wasik-Szczepanek, Ewa $u Dept. Hematooncology and Bone Marrow Transplantation, Medical University in Lublin, Lublin, Poland
- 700 1_
- $a Xu, Zhenshu $u Fujian Provincial Key Laboratory of Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, China
- 700 1_
- $a Yagci, Munci $u Gazi University Medical Faculty, Ankara, Turkey
- 700 1_
- $a Yañez, Lucrecia $u Department of Hematology, University Hospital Marqués de Valdecilla, Santander, Spain $u Department of Hematological Malignancies and Stem Cell Transplantation, Research Institute of Marques de Valdecilla (IDIVAL), Santander, Spain
- 700 1_
- $a Yassin, Mohamed $u Hematology Section, Department of Medical Oncology, National Center for Cancer Care and Research, Doha, Qatar
- 700 1_
- $a Zuchnicka, Jana $u Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic
- 700 1_
- $a Angelopoulou, Maria $u Haematology, University of Athens, Laikon General Hospital, Athens, Greece
- 700 1_
- $a Antic, Darko $u Clinic for Hematology, University Clinical Center of Serbia, Belgrade, Serbia $u Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- 700 1_
- $a Biderman, Bella $u Department of Molecular Hematology, National Medical Research Center for Hematology, Moscow, Russia
- 700 1_
- $a Catherwood, Mark $u Clinical Haematology, Belfast City Hospital, Belfast, United Kingdom
- 700 1_
- $a Claus, Rainer $u Pathology, Faculty of Medicine, University of Augsburg, Stenglinstrasse 2, Augsburg 86156, Germany $u Faculty of Medicine, Comprehensive Cancer Center Augsburg, University of Augsburg, Stenglinstrasse 2, Augsburg 86156, Germany
- 700 1_
- $a Coscia, Marta $u Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino and Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy
- 700 1_
- $a Cuneo, Antonio $u St. Anna University Hospital, Ferrara, Italy
- 700 1_
- $a Demirkan, Fatih $u Division of Hematology, Dokuz Eylul University, Izmir, Turkey
- 700 1_
- $a Espinet, Blanca $u Molecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar and Translational Research on Hematological Neoplasms Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain
- 700 1_
- $a Gaidano, Gianluca $u Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
- 700 1_
- $a Kalashnikova, Olga B $u Federal State Budgetary Educational Institution of Higher Education Academician I.P. Pavlov First St. Petersburg State Medical University of the Ministry of Healthcare of Russian Federation, St. Petersburg, Russia
- 700 1_
- $a Laurenti, Luca $u Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy $u Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- 700 1_
- $a Nikitin, Eugene $u Department of Hematology, Oncology, and Chemotherapy, S. P. Botkin's City Hospital, Moscow, Russia
- 700 1_
- $a Pangalis, Gerassimos A $u Department of Haematology, Athens Medical Center-Psychikon Branch, Athens, Greece
- 700 1_
- $a Panagiotidis, Panagiotis $u Department of Hematology and Bone Marrow Transplantation Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
- 700 1_
- $a Popov, Viola Maria $u Hematology Department, Colentina Clinical Hospital, Bucharest, Romania
- 700 1_
- $a Pospisilova, Sarka $u Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic $u Department of Internal Medicine - Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
- 700 1_
- $a Sportoletti, Paolo $u Institute of Hematology and Center for Hemato-Oncology Research, University of Perugia and Santa Maria della Misericordia Hospital, Perugia, Italy
- 700 1_
- $a Stavroyianni, Niki $u Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece
- 700 1_
- $a Tam, Constantine $u Peter MacCallum Cancer Centre, St Vincent's Hospital, University of Melbourne, Melbourne, VIC 3000, Australia
- 700 1_
- $a Trentin, Livio $u Hematology and Clinical Immunology Unit, Department of Medicine, University of Padova, Padova, Italy
- 700 1_
- $a Chatzidimitriou, Anastasia $u Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece
- 700 1_
- $a Bosch, Francesc $u Department of Haematology, University Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain
- 700 1_
- $a Doubek, Michael $u Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic $u Department of Internal Medicine - Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
- 700 1_
- $a Ghia, Paolo $u Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy
- 700 1_
- $a Stamatopoulos, Kostas $u Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece
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