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