Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONYResearch in context
Summary: 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. Meth...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | EClinicalMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537023004844 |
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| author | Thomas Chatzikonstantinou Lydia Scarfò Georgios Karakatsoulis Eva Minga Dimitra Chamou Gloria Iacoboni Jana Kotaskova Christos Demosthenous Lukas Smolej Stephen Mulligan Miguel Alcoceba Salem Al-Shemari Thérèse Aurran-Schleinitz Francesca Bacchiarri Mar Bellido Fontanet Bijou Anne Calleja Angeles Medina Mehreen Ali Khan Ramona Cassin Sofia Chatzileontiadou Rosa Collado Amy Christian Zadie Davis Maria Dimou David Donaldson Gimena Dos Santos Barbara Dreta Maria Efstathopoulou Shaimaa El-Ashwah Alicia Enrico Alberto Fresa Sara Galimberti Andrea Galitzia Rocío García-Serra Eva Gimeno Isabel González-Gascón-y-Marín Alessandro Gozzetti Valerio Guarente Romain Guieze Ajay Gogia Ritu Gupta Sean Harrop Eleftheria Hatzimichael Yair Herishanu José-Ángel Hernández-Rivas Luca Inchiappa Ozren Jaksic Susanne Janssen Elżbieta Kalicińska Laribi Kamel Volkan Karakus Arnon P. Kater Bonnie Kho Maria Kislova Eliana Konstantinou Maya Koren-Michowitz Ioannis Kotsianidis Robert J. Kreitman Jorge Labrador Deepesh Lad Mark-David Levin Ilana Levy Thomas Longval Alberto Lopez-Garcia Juan Marquet Lucia Martin-Rodríguez Marc Maynadié Stanislava Maslejova Carlota Mayor-Bastida Biljana Mihaljevic Ivana Milosevic Fatima Miras Riccardo Moia Marta Morawska Roberta Murru Uttam Kumar Nath Almudena Navarro-Bailón Ana C. Oliveira Jacopo Olivieri David Oscier Irina Panovska-Stavridis Maria Papaioannou Tomas Papajík Zuzana Kubova Punyarat Phumphukhieo Cheyenne Pierie Anna Puiggros Lata Rani Gianluigi Reda Gian Matteo Rigolin Rosa Ruchlemer Marcos Daniel de Deus Santos Mattia Schipani Annett Schiwitza Yandong Shen Martin Simkovic Svetlana Smirnova Dina Sameh Abdelrahman Soliman Martin Spacek Tamar Tadmor Kristina Tomic Eric Tse Theodoros Vassilakopoulos Andrea Visentin Candida Vitale Julia von Tresckow George Vrachiolias Vojin Vukovic Renata Walewska Ewa Wasik-Szczepanek Zhenshu Xu Munci Yagci Lucrecia Yañez Mohamed Yassin Jana Zuchnicka Maria Angelopoulou Darko Antic Bella Biderman Mark Catherwood Rainer Claus Marta Coscia Antonio Cuneo Fatih Demirkan Blanca Espinet Gianluca Gaidano Olga B. Kalashnikova Luca Laurenti Eugene Nikitin Gerassimos A. Pangalis Panagiotis Panagiotidis Viola Maria Popov Sarka Pospisilova Paolo Sportoletti Niki Stavroyianni Constantine Tam Livio Trentin Anastasia Chatzidimitriou Francesc Bosch Michael Doubek Paolo Ghia Kostas Stamatopoulos |
| author_facet | Thomas Chatzikonstantinou Lydia Scarfò Georgios Karakatsoulis Eva Minga Dimitra Chamou Gloria Iacoboni Jana Kotaskova Christos Demosthenous Lukas Smolej Stephen Mulligan Miguel Alcoceba Salem Al-Shemari Thérèse Aurran-Schleinitz Francesca Bacchiarri Mar Bellido Fontanet Bijou Anne Calleja Angeles Medina Mehreen Ali Khan Ramona Cassin Sofia Chatzileontiadou Rosa Collado Amy Christian Zadie Davis Maria Dimou David Donaldson Gimena Dos Santos Barbara Dreta Maria Efstathopoulou Shaimaa El-Ashwah Alicia Enrico Alberto Fresa Sara Galimberti Andrea Galitzia Rocío García-Serra Eva Gimeno Isabel González-Gascón-y-Marín Alessandro Gozzetti Valerio Guarente Romain Guieze Ajay Gogia Ritu Gupta Sean Harrop Eleftheria Hatzimichael Yair Herishanu José-Ángel Hernández-Rivas Luca Inchiappa Ozren Jaksic Susanne Janssen Elżbieta Kalicińska Laribi Kamel Volkan Karakus Arnon P. Kater Bonnie Kho Maria Kislova Eliana Konstantinou Maya Koren-Michowitz Ioannis Kotsianidis Robert J. Kreitman Jorge Labrador Deepesh Lad Mark-David Levin Ilana Levy Thomas Longval Alberto Lopez-Garcia Juan Marquet Lucia Martin-Rodríguez Marc Maynadié Stanislava Maslejova Carlota Mayor-Bastida Biljana Mihaljevic Ivana Milosevic Fatima Miras Riccardo Moia Marta Morawska Roberta Murru Uttam Kumar Nath Almudena Navarro-Bailón Ana C. Oliveira Jacopo Olivieri David Oscier Irina Panovska-Stavridis Maria Papaioannou Tomas Papajík Zuzana Kubova Punyarat Phumphukhieo Cheyenne Pierie Anna Puiggros Lata Rani Gianluigi Reda Gian Matteo Rigolin Rosa Ruchlemer Marcos Daniel de Deus Santos Mattia Schipani Annett Schiwitza Yandong Shen Martin Simkovic Svetlana Smirnova Dina Sameh Abdelrahman Soliman Martin Spacek Tamar Tadmor Kristina Tomic Eric Tse Theodoros Vassilakopoulos Andrea Visentin Candida Vitale Julia von Tresckow George Vrachiolias Vojin Vukovic Renata Walewska Ewa Wasik-Szczepanek Zhenshu Xu Munci Yagci Lucrecia Yañez Mohamed Yassin Jana Zuchnicka Maria Angelopoulou Darko Antic Bella Biderman Mark Catherwood Rainer Claus Marta Coscia Antonio Cuneo Fatih Demirkan Blanca Espinet Gianluca Gaidano Olga B. Kalashnikova Luca Laurenti Eugene Nikitin Gerassimos A. Pangalis Panagiotis Panagiotidis Viola Maria Popov Sarka Pospisilova Paolo Sportoletti Niki Stavroyianni Constantine Tam Livio Trentin Anastasia Chatzidimitriou Francesc Bosch Michael Doubek Paolo Ghia Kostas Stamatopoulos |
| author_sort | Thomas Chatzikonstantinou |
| collection | DOAJ |
| description | Summary: 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/EFPIA Innovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026. |
| first_indexed | 2024-03-09T14:25:39Z |
| format | Article |
| id | doaj.art-406b5cb078414ff6beadc58b69ce0c26 |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-03-09T14:25:39Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-406b5cb078414ff6beadc58b69ce0c262023-11-28T07:26:53ZengElsevierEClinicalMedicine2589-53702023-11-0165102307Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONYResearch in contextThomas Chatzikonstantinou0Lydia Scarfò1Georgios Karakatsoulis2Eva Minga3Dimitra Chamou4Gloria Iacoboni5Jana Kotaskova6Christos Demosthenous7Lukas Smolej8Stephen Mulligan9Miguel Alcoceba10Salem Al-Shemari11Thérèse Aurran-Schleinitz12Francesca Bacchiarri13Mar Bellido14Fontanet Bijou15Anne Calleja16Angeles Medina17Mehreen Ali Khan18Ramona Cassin19Sofia Chatzileontiadou20Rosa Collado21Amy Christian22Zadie Davis23Maria Dimou24David Donaldson25Gimena Dos Santos26Barbara Dreta27Maria Efstathopoulou28Shaimaa El-Ashwah29Alicia Enrico30Alberto Fresa31Sara Galimberti32Andrea Galitzia33Rocío García-Serra34Eva Gimeno35Isabel González-Gascón-y-Marín36Alessandro Gozzetti37Valerio Guarente38Romain Guieze39Ajay Gogia40Ritu Gupta41Sean Harrop42Eleftheria Hatzimichael43Yair Herishanu44José-Ángel Hernández-Rivas45Luca Inchiappa46Ozren Jaksic47Susanne Janssen48Elżbieta Kalicińska49Laribi Kamel50Volkan Karakus51Arnon P. Kater52Bonnie Kho53Maria Kislova54Eliana Konstantinou55Maya Koren-Michowitz56Ioannis Kotsianidis57Robert J. Kreitman58Jorge Labrador59Deepesh Lad60Mark-David Levin61Ilana Levy62Thomas Longval63Alberto Lopez-Garcia64Juan Marquet65Lucia Martin-Rodríguez66Marc Maynadié67Stanislava Maslejova68Carlota Mayor-Bastida69Biljana Mihaljevic70Ivana Milosevic71Fatima Miras72Riccardo Moia73Marta Morawska74Roberta Murru75Uttam Kumar Nath76Almudena Navarro-Bailón77Ana C. Oliveira78Jacopo Olivieri79David Oscier80Irina Panovska-Stavridis81Maria Papaioannou82Tomas Papajík83Zuzana Kubova84Punyarat Phumphukhieo85Cheyenne Pierie86Anna Puiggros87Lata Rani88Gianluigi Reda89Gian Matteo Rigolin90Rosa Ruchlemer91Marcos Daniel de Deus Santos92Mattia Schipani93Annett Schiwitza94Yandong Shen95Martin Simkovic96Svetlana Smirnova97Dina Sameh Abdelrahman Soliman98Martin Spacek99Tamar Tadmor100Kristina Tomic101Eric Tse102Theodoros Vassilakopoulos103Andrea Visentin104Candida Vitale105Julia von Tresckow106George Vrachiolias107Vojin Vukovic108Renata Walewska109Ewa Wasik-Szczepanek110Zhenshu Xu111Munci Yagci112Lucrecia Yañez113Mohamed Yassin114Jana Zuchnicka115Maria Angelopoulou116Darko Antic117Bella Biderman118Mark Catherwood119Rainer Claus120Marta Coscia121Antonio Cuneo122Fatih Demirkan123Blanca Espinet124Gianluca Gaidano125Olga B. Kalashnikova126Luca Laurenti127Eugene Nikitin128Gerassimos A. Pangalis129Panagiotis Panagiotidis130Viola Maria Popov131Sarka Pospisilova132Paolo Sportoletti133Niki Stavroyianni134Constantine Tam135Livio Trentin136Anastasia Chatzidimitriou137Francesc Bosch138Michael Doubek139Paolo Ghia140Kostas Stamatopoulos141Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, GreeceUniversità Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, ItalyInstitute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece; Department of Mathematics, University of Ioannina, Ioannina, GreeceInstitute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, GreeceInstitute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, GreeceDepartment of Haematology, University Hospital Vall d'Hebron, Autonomous University, Barcelona, SpainCentral European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic; Department of Internal Medicine - Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech RepublicHematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece4th Department of Internal Medicine-Haematology, University Hospital and Faculty of Medicine, Hradec Králové, Czech RepublicRoyal North Shore Hospital, Sydney, NSW, AustraliaDepartment of Haematology, University Hospital of Salamanca (HUS-IBSAL), CIBERONC (CB16/12/00233) and Cancer Research Centre (CIC-IBMCC, USAL-CSIC), Salamanca, SpainFaculty of Medicine, Department of Medicine, Kuwait University, Kuwait City, KuwaitDepartment of Hemato-Oncology, Institut Paoli Calmettes, Marseille, FranceDivision of Hematology, University of Siena, Siena, ItalyHematology Department, University Medical Center Groningen, University of Groningen, Groningen, the NetherlandsInstitut Bergonié, Bordeaux, FranceDepartment of Hemato-Oncology, Institut Paoli Calmettes, Marseille, FranceHospital Costa del Sol, Málaga, SpainDepartment of Hematology and Stem Cell Transplant, Armed Forces Bone Marrow Transplant Center/National Institute of Blood and Marrow Transplant, Rawalpindi, PakistanHematology Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico of Milan, Milan, ItalyHematology Unit, 1st Dept of Internal Medicine, AUTH, AHEPA Hospital, Thessaloniki, GreeceServicio de Hematología, Consorcio Hospital General Universitario de Valencia, Fundación de Investigación Hospital General Universitario de Valencia, Valencia, SpainDepartment of Haematology, Royal Bournemouth Hospital, Bournemouth, United KingdomDepartment of Haematology, Royal Bournemouth Hospital, Bournemouth, United KingdomDepartment of Hematology and Bone Marrow Transplantation Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, GreeceClinical Haematology, Belfast City Hospital, Belfast, United KingdomHospital de Clinicas, Montevideo, UruguayDivision of Hematology, Department of Internal Medicine, University Hospital Center Zagreb, Zagreb, CroatiaDepartment of Haematology, Athens Medical Center-Psychikon Branch, Athens, GreeceOncology Center, Mansoura University, Mansoura, EgyptHospital Italiano La Plata, Buenos Aires, ArgentinaSezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy; Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalySection of Hematology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyHematology and Stem Cell Transplantation Unit, Ospedale Oncologico A. Businco, ARNAS ''G. Brotzu'', Cagliari, ItalyServicio de Hematología, Consorcio Hospital General Universitario de Valencia, Fundación de Investigación Hospital General Universitario de Valencia, Valencia, SpainDepartment of Hematology, Hospital del Mar, Barcelona, SpainHematology Department, Infanta Leonor University Hospital, Madrid, SpainDivision of Hematology, University of Siena, Siena, ItalyInstitute of Hematology and Center for Hemato-Oncology Research, University of Perugia and Santa Maria della Misericordia Hospital, Perugia, ItalyDepartment of Hematology and Cell Therapy, Estaing University Hospital, Clermont-Ferrand, FranceLaboratory Oncology Unit, Dr. B.R.A. IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, IndiaLaboratory Oncology Unit, Dr. B.R.A. IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, IndiaPeter MacCallum Cancer Centre, St Vincent's Hospital, University of Melbourne, Melbourne, VIC 3000, AustraliaFaculty of Medicine, Department of Haematology, School of Health Sciences, University of Ioannina, Stavros Niarchos Avenue, Ioannina 45110, GreeceDepartment of Hematology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, IsraelHematology Department, Infanta Leonor University Hospital, Madrid, SpainDepartment of Hemato-Oncology, Institut Paoli Calmettes, Marseille, FranceDepartment of Hematology, University Hospital Dubrava, Zagreb, CroatiaDept of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the NetherlandsDepartment and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation Wroclaw Medical University, Wroclaw, PolandDepartment of Hematology, Centre Hospitalier Le Mans, Le Mans, FranceAntalya Training and Research Hospital, Antalya, TurkeyDept of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the NetherlandsDepartment of Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, ChinaDepartment of Hematology, Oncology, and Chemotherapy, S. P. Botkin's City Hospital, Moscow, RussiaHaematology, University of Athens, Laikon General Hospital, Athens, GreeceDepartment of Hematology, Shamir Medical Center, Zerifin, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, IsraelDepartment of Hematology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, GreeceLaboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USADepartment of Hematology, Hospital Universitario de Burgos, Burgos, SpainDepartment of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, the NetherlandsHematology, Bnai-Zion Medical Center, Haifa, IsraelService d'Hématologie Oncologie, Centre Hospitalier de Versailles, Le Chesnay, FranceFundacion Jimenez Diaz University Hospital, Health Research Institute IIS-FJD, Madrid, SpainHematology Department, Ramón y Cajal University Hospital, Madrid, SpainDepartment of Haematology, University Hospital Vall d'Hebron, Autonomous University, Barcelona, SpainBiological Haematology Department, Dijon Bourgogne University Hospital, Haematological Malignancies Registry, LNC UMR 1231, Dijon 21000, FranceDepartment of Internal Medicine - Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech RepublicHaematology Department, Hospital Universitario de La Princesa, Madrid, SpainClinic for Hematology, University Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, SerbiaFaculty of Medicine, Clinical Centre of Vojvodina, University of Novi Sad, Novi Sad, SerbiaHematology Department, Hospital Universitario 12 de Octubre, Madrid, SpainDivision of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, ItalyExperimental Hematooncology Department, Medical University of Lublin, Lublin, Poland; Hematology Department, St. John's Cancer Center, Lublin, PolandHematology and Stem Cell Transplantation Unit, Ospedale Oncologico A. Businco, ARNAS ''G. Brotzu'', Cagliari, ItalyDepartment of Medical Oncology & Hematology, All India Institute of Medical Sciences, Rishikesh, IndiaDepartment of Haematology, University Hospital of Salamanca (HUS-IBSAL), CIBERONC (CB16/12/00233) and Cancer Research Centre (CIC-IBMCC, USAL-CSIC), Salamanca, SpainDepartment of Clinical Hematology, ICO, Hospital Duran i Reynals, IDIBELL, Barcelona, SpainHematology Clinic, ASUFC, Udine, ItalyDepartment of Haematology, Royal Bournemouth Hospital, Bournemouth, United KingdomMedical Faculty, University Clinic of Hematology, University Ss. Cyril and Methodius, Skopje, North MacedoniaHematology Unit, 1st Dept of Internal Medicine, AUTH, AHEPA Hospital, Thessaloniki, GreeceFaculty of Medicine and Dentistry, Department of Hemato-Oncology, Palacký University and University Hospital Olomouc, Olomouc, Czech RepublicFaculty of Medicine and Dentistry, Department of Hemato-Oncology, Palacký University and University Hospital Olomouc, Olomouc, Czech RepublicHull York Medical School, Hull, United KingdomDept of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the NetherlandsMolecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar and Translational Research on Hematological Neoplasms Group, Hospital del Mar Research Institute (IMIM), Barcelona, SpainLaboratory Oncology Unit, Dr. B.R.A. IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, IndiaHematology Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico of Milan, Milan, ItalySt. Anna University Hospital, Ferrara, ItalyDepartment of Hematology, Shaare-Zedek Medical Center, Affiliated with the Hebrew University Medical School, Jerusalem, IsraelInternal Medicine Department, Universidade Federal do Espírito Santo, Vila Velha, ES, BrazilDivision of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, ItalyHematology and Oncology, Faculty of Medicine, University of Augsburg, Stenglinstrasse 2, Augsburg 86156, GermanyRoyal North Shore Hospital, Sydney, NSW, Australia4th Department of Internal Medicine-Haematology, University Hospital and Faculty of Medicine, Hradec Králové, Czech RepublicConsultative Hematology Department with a Day Hospital for Intensive High-Dose Chemotherapy, National Medical Research Center for Hematology, Moscow, RussiaHematopathology Laboratory, Hamad Medical Corporation, Doha, QatarFirst Faculty of Medicine, 1st Department of Medicine - Hematology, Charles University and General Hospital in Prague, Czech RepublicHematology, Bnai-Zion Medical Center, Haifa, IsraelClinic for Hematology, University Clinical Center of Serbia, Belgrade, SerbiaDepartment of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, ChinaHaematology, University of Athens, Laikon General Hospital, Athens, GreeceHematology and Clinical Immunology Unit, Department of Medicine, University of Padova, Padova, ItalyDivision 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, ItalyClinic for Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Hematology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, GreeceClinic for Hematology, University Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of Haematology, Royal Bournemouth Hospital, Bournemouth, United KingdomDept. Hematooncology and Bone Marrow Transplantation, Medical University in Lublin, Lublin, PolandFujian Provincial Key Laboratory of Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, ChinaGazi University Medical Faculty, Ankara, TurkeyDepartment of Hematology, University Hospital Marqués de Valdecilla, Santander, Spain; Department of Hematological Malignancies and Stem Cell Transplantation, Research Institute of Marques de Valdecilla (IDIVAL), Santander, SpainHematology Section, Department of Medical Oncology, National Center for Cancer Care and Research, Doha, QatarDepartment of Haematooncology, University Hospital Ostrava, Ostrava, Czech RepublicHaematology, University of Athens, Laikon General Hospital, Athens, GreeceClinic for Hematology, University Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of Molecular Hematology, National Medical Research Center for Hematology, Moscow, RussiaClinical Haematology, Belfast City Hospital, Belfast, United KingdomPathology, Faculty of Medicine, University of Augsburg, Stenglinstrasse 2, Augsburg 86156, Germany; Faculty of Medicine, Comprehensive Cancer Center Augsburg, University of Augsburg, Stenglinstrasse 2, Augsburg 86156, GermanyDivision 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, ItalySt. Anna University Hospital, Ferrara, ItalyDivision of Hematology, Dokuz Eylul University, Izmir, TurkeyMolecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar and Translational Research on Hematological Neoplasms Group, Hospital del Mar Research Institute (IMIM), Barcelona, SpainDivision of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, ItalyFederal 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, RussiaSezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy; Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyDepartment of Hematology, Oncology, and Chemotherapy, S. P. Botkin's City Hospital, Moscow, RussiaDepartment of Haematology, Athens Medical Center-Psychikon Branch, Athens, GreeceDepartment of Hematology and Bone Marrow Transplantation Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, GreeceHematology Department, Colentina Clinical Hospital, Bucharest, RomaniaCentral European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic; Department of Internal Medicine - Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech RepublicInstitute of Hematology and Center for Hemato-Oncology Research, University of Perugia and Santa Maria della Misericordia Hospital, Perugia, ItalyHematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, GreecePeter MacCallum Cancer Centre, St Vincent's Hospital, University of Melbourne, Melbourne, VIC 3000, AustraliaHematology and Clinical Immunology Unit, Department of Medicine, University of Padova, Padova, ItalyInstitute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, GreeceDepartment of Haematology, University Hospital Vall d'Hebron, Autonomous University, Barcelona, SpainCentral European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic; Department of Internal Medicine - Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech RepublicUniversità Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy; Corresponding author. Università Vita Salute San Raffaele and IRCCS Ospedale San Raffaele, Via Olgettina 58, Milan 20132, Italy.Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, GreeceSummary: 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/EFPIA Innovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026.http://www.sciencedirect.com/science/article/pii/S2589537023004844Chronic lymphocytic leukemiaOther malignanciesOther cancersSecond primary malignancies |
| spellingShingle | Thomas Chatzikonstantinou Lydia Scarfò Georgios Karakatsoulis Eva Minga Dimitra Chamou Gloria Iacoboni Jana Kotaskova Christos Demosthenous Lukas Smolej Stephen Mulligan Miguel Alcoceba Salem Al-Shemari Thérèse Aurran-Schleinitz Francesca Bacchiarri Mar Bellido Fontanet Bijou Anne Calleja Angeles Medina Mehreen Ali Khan Ramona Cassin Sofia Chatzileontiadou Rosa Collado Amy Christian Zadie Davis Maria Dimou David Donaldson Gimena Dos Santos Barbara Dreta Maria Efstathopoulou Shaimaa El-Ashwah Alicia Enrico Alberto Fresa Sara Galimberti Andrea Galitzia Rocío García-Serra Eva Gimeno Isabel González-Gascón-y-Marín Alessandro Gozzetti Valerio Guarente Romain Guieze Ajay Gogia Ritu Gupta Sean Harrop Eleftheria Hatzimichael Yair Herishanu José-Ángel Hernández-Rivas Luca Inchiappa Ozren Jaksic Susanne Janssen Elżbieta Kalicińska Laribi Kamel Volkan Karakus Arnon P. Kater Bonnie Kho Maria Kislova Eliana Konstantinou Maya Koren-Michowitz Ioannis Kotsianidis Robert J. Kreitman Jorge Labrador Deepesh Lad Mark-David Levin Ilana Levy Thomas Longval Alberto Lopez-Garcia Juan Marquet Lucia Martin-Rodríguez Marc Maynadié Stanislava Maslejova Carlota Mayor-Bastida Biljana Mihaljevic Ivana Milosevic Fatima Miras Riccardo Moia Marta Morawska Roberta Murru Uttam Kumar Nath Almudena Navarro-Bailón Ana C. Oliveira Jacopo Olivieri David Oscier Irina Panovska-Stavridis Maria Papaioannou Tomas Papajík Zuzana Kubova Punyarat Phumphukhieo Cheyenne Pierie Anna Puiggros Lata Rani Gianluigi Reda Gian Matteo Rigolin Rosa Ruchlemer Marcos Daniel de Deus Santos Mattia Schipani Annett Schiwitza Yandong Shen Martin Simkovic Svetlana Smirnova Dina Sameh Abdelrahman Soliman Martin Spacek Tamar Tadmor Kristina Tomic Eric Tse Theodoros Vassilakopoulos Andrea Visentin Candida Vitale Julia von Tresckow George Vrachiolias Vojin Vukovic Renata Walewska Ewa Wasik-Szczepanek Zhenshu Xu Munci Yagci Lucrecia Yañez Mohamed Yassin Jana Zuchnicka Maria Angelopoulou Darko Antic Bella Biderman Mark Catherwood Rainer Claus Marta Coscia Antonio Cuneo Fatih Demirkan Blanca Espinet Gianluca Gaidano Olga B. Kalashnikova Luca Laurenti Eugene Nikitin Gerassimos A. Pangalis Panagiotis Panagiotidis Viola Maria Popov Sarka Pospisilova Paolo Sportoletti Niki Stavroyianni Constantine Tam Livio Trentin Anastasia Chatzidimitriou Francesc Bosch Michael Doubek Paolo Ghia Kostas Stamatopoulos Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONYResearch in context EClinicalMedicine Chronic lymphocytic leukemia Other malignancies Other cancers Second primary malignancies |
| title | Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONYResearch in context |
| title_full | Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONYResearch in context |
| title_fullStr | Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONYResearch in context |
| title_full_unstemmed | Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONYResearch in context |
| title_short | Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONYResearch in context |
| title_sort | other malignancies in the history of cll an international multicenter study conducted by eric the european research initiative on cll in harmonyresearch in context |
| topic | Chronic lymphocytic leukemia Other malignancies Other cancers Second primary malignancies |
| url | http://www.sciencedirect.com/science/article/pii/S2589537023004844 |
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