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oai:recercat.cat:11351/108472025-10-24T10:33:41Zcom_2072_378070com_2072_378040col_2072_378092

2025-10-24T10:33:41Z urn:hdl:11351/10847 Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY Minga, Eva Chamou, Dimitra Chatzikonstantinou, Thomas Scarfo', Lydia KARAKATSOULIS, GEORGIOS IACOBONI, GLORIA Leucèmia limfocítica crònica Càncer - Factors de risc DISEASES::Hemic and Lymphatic Diseases::Lymphatic Diseases::Lymphoproliferative Disorders::Leukemia, Lymphoid::Leukemia, B-Cell::Leukemia, Lymphocytic, Chronic, B-Cell ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors DISEASES::Neoplasms::Neoplasms, Second Primary ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades linfáticas::trastornos linfoproliferativos::leucemia linfoide::leucemia de células B::leucemia linfocítica crónica de células B TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo ENFERMEDADES::neoplasias::neoplasias primarias secundarias Chronic lymphocytic leukemia Leucèmia limfocítica crònica Leucemia linfocítica crónica 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. This project was supported in part by AbbVie; EU/EFPIA Innovative Medicines Initiative [2] Joint Undertaking HARMONY grant n° 116026; the Hellenic Precision Medicine Network in Oncology; MH-CZ_AZV_NU23-03-00401; MH CZ DRO (FNBr, 65269705); MH CZ DRO (FNOl, 00098892), program COOPERATIO (research area ONCO), and NPO-NUVR LX22NPO5102. Munci Yagci was provided with study materials. 2025-10-24T10:33:41Z 2025-10-24T10:33:41Z 2024-01-15T07:46:21Z 2024-01-15T07:46:21Z 2023-11 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/10847 eClinicalMedicine;65 https://doi.org/10.1016/j.eclinm.2023.102307 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Elsevier Scientia