Article Dans Une Revue EClinicalMedicine Année : 2023

Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY

Thomas Chatzikonstantinou (1) , Lydia Scarfò (2) , Georgios Karakatsoulis (3, 4) , Eva Minga (5) , Dimitra Chamou (1) , Gloria Iacoboni (6) , Jana Kotaskova (7, 8) , Christos Demosthenous (9) , Lukas Smolej (10) , Stephen Mulligan (11) , Miguel Alcoceba (12) , Salem Al-Shemari (13) , Thérèse Aurran-Schleinitz (14) , Francesca Bacchiarri (15) , Mar Bellido (16) , Fontanet Bijou (17) , Anne Calleja (18, 19) , Angeles Medina (20) , Mehreen Ali Khan (21) , Ramona Cassin (22) , Sofia Chatzileontiadou (23) , Rosa Collado (24) , Amy Christian (25) , Zadie Davis (25) , Maria Dimou (26) , David Donaldson (27) , Gimena Dos Santos (28) , Barbara Dreta (29) , Maria Efstathopoulou (26) , Shaimaa El-Ashwah (30) , Alicia Enrico (31) , Alberto Fresa (32, 33) , Sara Galimberti (34) , Andrea Galitzia (35) , Rocío García-Serra (36) , Eva Gimeno (37) , Isabel González-Gascón-Y-Marín (38) , Alessandro Gozzetti (39) , Valerio Guarente (40, 41) , Romain Guieze (42, 43) , Ajay Gogia (44) , Ritu Gupta (44) , Sean Harrop (45) , Eleftheria Hatzimichael (4) , Yair Herishanu (46) , José-Ángel Hernández-Rivas (38) , Luca Inchiappa (14) , Ozren Jaksic (47) , Susanne Janssen (48, 49) , Elżbieta Kalicińska (50) , Kamel Laribi (51) , Volkan Karakus (52) , Arnon Kater (49) , Bonnie Kho (53) , Maria Kislova (54) , Eliana Konstantinou (26, 55) , Maya Koren-Michowitz (56, 57) , Ioannis Kotsianidis (58, 59) , Robert Kreitman (60) , Jorge Labrador (61) , Deepesh Lad (62) , Mark-David Levin (63) , Ilana Levy (64) , Thomas Longval (65) , Alberto Lopez-Garcia (66) , Juan Marquet (67) , Lucia Martin-Rodríguez (6, 68) , Marc Maynadié (69, 70) , Stanislava Maslejova (7, 8) , Carlota Mayor-Bastida (71) , Biljana Mihaljevic (72, 73) , Ivana Milosevic (74) , Fatima Miras (75) , Riccardo Moia (76) , Marta Morawska (77) , Roberta Murru (78) , Uttam Kumar Nath (44) , Almudena Navarro-Bailón (79, 80) , Ana Oliveira (81, 82) , Jacopo Olivieri (83) , David Oscier (25) , Irina Panovska-Stavridis (84) , Maria Papaioannou (85) , Tomas Papajík (86, 87) , Zuzana Kubova (86, 87) , Punyarat Phumphukhieo (88) , Cheyenne Pierie (48, 49) , Anna Puiggros (37, 89) , Lata Rani (44) , Gianluigi Reda (90) , Gian Matteo Rigolin (91) , Rosa Ruchlemer (92, 93) , Marcos Daniel de Deus Santos (94) , Mattia Schipani (95) , Annett Schiwitza (96) , Yandong Shen (11) , Martin Simkovic (97) , Svetlana Smirnova (98) , Dina Sameh Abdelrahman Soliman (99) , Martin Spacek (100, 101) , Tamar Tadmor (102) , Kristina Tomic (72) , Eric Tse (103) , Theodoros Vassilakopoulos (104) , Andrea Visentin (105) , Candida Vitale (106, 107) , Julia von Tresckow (108, 109, 110) , George Vrachiolias (58, 111) , Vojin Vukovic (72, 73) , Renata Walewska (25) , Ewa Wasik-Szczepanek (112) , Zhenshu Xu (113) , Munci Yagci (114) , Lucrecia Yañez (115) , Mohamed Yassin (116) , Jana Zuchnicka (117) , Maria Angelopoulou (26) , Darko Antic (73) , Bella Biderman (98) , Mark Catherwood (27) , Rainer Claus (118) , Marta Coscia (107, 106) , Antonio Cuneo (91) , Fatih Demirkan (119) , Blanca Espinet (37, 89) , Gianluca Gaidano (95) , Olga Kalashnikova (120) , Luca Laurenti (33, 32) , Eugene Nikitin (54, 121) , Gerassimos Pangalis (26) , Panagiotis Panagiotidis (26) , Viola Maria Popov (122) , Sarka Pospisilova (7, 8) , Paolo Sportoletti (40, 41) , Niki Stavroyianni (123) , Constantine Tam (124, 125) , Livio Trentin (105) , Anastasia Chatzidimitriou (1, 126) , Francesc Bosch (68) , Michael Doubek (8, 127, 7) , Paolo Ghia (128, 2) , Kostas Stamatopoulos (1)
1 CERTH - Centre for Research and Technology Hellas
2 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
3 INAB - Institute of Applied Biosciences [Thessaloniki, Greece]
4 University of Ioannina
5 Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece;
6 Vall d'Hebron University Hospital [Barcelona]
7 University Hospital Brno
8 MU / MUNI - Masaryk University [Brno] = Masarykova univerzita [Brno] = Université Masaryk [Brno]
9 Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece
10 Faculty of Medicine in Hradec Kralove [Republique Tchèque]
11 RNSH - Royal North Shore Hospital
12 Universidad de Salamanca [España] = University of Salamanca [Spain]
13 Kuwait University
14 IPC - Institut Paoli-Calmettes
15 University Hospital of Siena
16 University of Groningen [Groningen]
17 Institut Bergonié [Bordeaux]
18 UCA Faculté Médecine - Université Côte d'Azur - Faculté de Médecine
19 CHU Nice - Centre Hospitalier Universitaire de Nice
20 Hospital Costa del Sol
21 National Institute of Blood Disease & Bone Marrow Transplantation Karachi, Pakistan. 7Faculty of Pharmacy, Ziauddin University Clifton Karachi, Pakistan.
22 IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico [Milano, Italia]
23 AHEPA University General Hospital [Thessaloniki]
24 Consorcio Hospital General Universitario de Valencia
25 UHD - University Hospitals Dorset NHS Foundation Trust [Bournemouth, UK]
26 University of Athens Medical School [Athens]
27 Belfast City Hospital
28 Hospital de Clínicas [Montevideo]
29 University Hospital Center, Zagreb, Croatia
30 Mansoura University [Egypt]
31 Hospital Italiano de Buenos Aires
32 Unicatt - Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma]
33 Fondazione Policlinico Universitario Agostino Gemelli IRCCS
34 Department of Oncology, Transplants and Advanced Technologies, Section of Hematology
35 ARNAS “Garibaldi, S. Luigi-Currò, Ascoli-Tomaselli”
36 Hospital General Universitario de Valencia
37 IMIM-Hospital del Mar
38 Hospital Universitario Infanta Leonor [Madrid]
39 Azienda Ospedaliera Universitaria Senese
40 UNIPG - Università degli Studi di Perugia = University of Perugia
41 Ospedale "Santa Maria della Misericordia" = University Hospital "Santa Maria della Misericordia"
42 CHU Clermont-Ferrand
43 CHELTER - Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias
44 All India Institute of Medical Sciences [New Delhi]
45 University of Melbourne
46 Tel Aviv Sourasky Medical Center [Tel Aviv]
47 Dubrava University Hospital - Zagreb School of Medicine [Zagreb, Croatia]
48 Amsterdam UMC - Amsterdam University Medical Centers
49 UvA - Universiteit van Amsterdam = University of Amsterdam
50 Wrocław Medical University
51 Centre Hospitalier Le Mans (CH Le Mans)
52 Medical Park Antalya Hospital [Turkey]
53 Pamela Youde Nethersole Eastern Hospital
54 2CHNSPB - City Clinical Hospital Named After S.P. Botkin [Moscow, Russian Federation]
55 Laikon General Hospital
56 Shamir Medical Center
57 TAU - Tel Aviv University
58 AUH - Alexandroupolis University Hospital [Alexandroupolis, Greece]
59 University of Thrace
60 NCI-NIH - National Cancer Institute [Bethesda]
61 Universidad de Burgos = University of Burgos
62 PGIMER - Postgraduate Institute of Medical Education & Research
63 Albert Schweitzer Hospital
64 UNIROUEN UFR Santé - UNIROUEN - UFR Santé
65 CHV - Centre Hospitalier de Versailles André Mignot
66 FJD - Hospital Universitario Fundación Jiménez Díaz [Madrid]
67 Ramón y Cajal University Hospital
68 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
69 EPI2THM - Épigénétique, épidémiologie et thérapies personnalisées des hémopathies malignes : EPI2THM (CTM UMR 1231)
70 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
71 Hospital Universitario de La Princesa
72 University Clinical Centre of Serbia
73 University of Belgrade [Belgrade]
74 University of Novi Sad
75 Hospital Universitario 12 de Octubre = University Hospital October 12 [Madrid]
76 UPO - Università degli Studi del Piemonte Orientale - Amedeo Avogadro
77 University Hospital Basel [Basel]
78 Gastroenterology Unit, ARNAS G. Brotzu, Cagliari, Italy.
79 CIBERONC - Centro de Investigación Biomédica en Red de Cáncer
80 USAL-CSIC - Laboratorio de Patología Molecular
81 RISE-Health
82 Universidade do Porto = University of Porto
83 General Manager of the entity Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), Italy.
84 UKIM - Ss. Cyril and Methodius University in Skopje / Универзитет „Св. Кирил и Методиј“ во Скопје [Skopje, Republic of North Macedonia]
85 University of Cyprus = Université de Chypre
86 Palacky University Olomouc
87 University Hospital Olomouc [Czech Republic]
88 HYMS - Hull York Medical School [York, UK]
89 Laboratoris de Citologia Hematológica/Citogenética Molecular. Servei de Patologia, GRETNHE
90 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
91 UniFE - Università degli Studi di Ferrara = University of Ferrara
92 The Hebrew University Hadassah Medical School
93 Shaare Zedek Medical Center
94 UFES - Universidade Federal do Espirito Santo
95 Amedeo Avogadro University of Eastern Piedmont
96 UNIA - Universität Augsburg [Deutschland] = University of Augsburg [Germany] = Université d'Augsbourg [Allemagne]
97 3. LF UK / 3rd Faculty of Medicine - 3. lékařská fakulta, Univerzita Karlova [Praha, Česká republika] = Third Faculty of Medicine, Charles University [Prague, Czech Republic]
98 RCMG - Research Centre for Medical Genetics [Moscow, Russia]
99 Hamad Medical Corporation [Doha, Qatar]
100 Institute of Phonetics of Charles University
101 VFN - General University Hospital in Prague
102 Bnai Zion Medical Center [Israël]
103 HKU - The University of Hong Kong
104 NKUA - National and Kapodistrian University of Athens
105 Unipd - Università degli Studi di Padova = University of Padua
106 A.O.U - Città della Salute e della Scienza di Torino
107 UNITO - Università degli studi di Torino = University of Turin
108 West German Cancer Center [Essen, Germany]
109 AöR - University Hospital Essen
110 Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
111 DUTH - Democritus University of Thrace
112 Medical University of Lublin
113 Fujian Medical University Union Hospital, Fujian Institute of Hematology, Fuzhou
114 Gazi University
115 IDIVAL - Marqués de Valdecilla Research Institute - Instituto de Investigación Marqués de Valdecilla [Santander]
116 CRF - Centre de Recherche Forestière [Maroc]
117 University Hospital Ostrava
118 Department of Cancer Epidemiology
119 DEÜ - Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir]
120 JPL - Jet Propulsion Laboratory
121 Russian Academy of Medical Sciences
122 Spitalul Clinic Colentina = Colentina Hospital [Bucharest, Romania]
123 General Hospital of Thessaloniki George Papanikolaou
124 Alfred Health
125 Monash University [Melbourne]
126 Karolinska Institutet = Karolinska Institute [Stockholm]
127 CEITEC MU - Central European Institute of Technology [Brno]
128 IRCCS Ospedale San Raffaele [Milan, Italy]
Stephen Mulligan
Eleftheria Hatzimichael
Munci Yagci
  • Fonction : Auteur

Résumé

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.

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inserm-05385722 , version 1 (27-11-2025)

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Thomas Chatzikonstantinou, Lydia Scarfò, Georgios Karakatsoulis, Eva Minga, Dimitra Chamou, et al.. Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY. EClinicalMedicine, 2023, 65, pp.102307. ⟨10.1016/j.eclinm.2023.102307⟩. ⟨inserm-05385722⟩
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