慢性淋巴细胞白血病病史中的其他恶性肿瘤：由欧洲慢性淋巴细胞白血病研究倡议组织（ERIC）在“和谐”研究中开展的一项国际多中心研究。
Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY.
作者信息
Chatzikonstantinou Thomas, Scarfò Lydia, Karakatsoulis Georgios, Minga Eva, Chamou Dimitra, Iacoboni Gloria, Kotaskova Jana, Demosthenous Christos, Smolej Lukas, Mulligan Stephen, Alcoceba Miguel, Al-Shemari Salem, Aurran-Schleinitz Thérèse, Bacchiarri Francesca, Bellido Mar, Bijou Fontanet, Calleja Anne, Medina Angeles, Khan Mehreen Ali, Cassin Ramona, Chatzileontiadou Sofia, Collado Rosa, Christian Amy, Davis Zadie, Dimou Maria, Donaldson David, Santos Gimena Dos, Dreta Barbara, Efstathopoulou Maria, El-Ashwah Shaimaa, Enrico Alicia, Fresa Alberto, Galimberti Sara, Galitzia Andrea, García-Serra Rocío, Gimeno Eva, González-Gascón-Y-Marín Isabel, Gozzetti Alessandro, Guarente Valerio, Guieze Romain, Gogia Ajay, Gupta Ritu, Harrop Sean, Hatzimichael Eleftheria, Herishanu Yair, Hernández-Rivas José-Ángel, Inchiappa Luca, Jaksic Ozren, Janssen Susanne, Kalicińska Elżbieta, Laribi Kamel, Karakus Volkan, Kater Arnon P, Kho Bonnie, Kislova Maria, Konstantinou Eliana, Koren-Michowitz Maya, Kotsianidis Ioannis, Kreitman Robert J, Labrador Jorge, Lad Deepesh, Levin Mark-David, Levy Ilana, Longval Thomas, Lopez-Garcia Alberto, Marquet Juan, Martin-Rodríguez Lucia, Maynadié Marc, Maslejova Stanislava, Mayor-Bastida Carlota, Mihaljevic Biljana, Milosevic Ivana, Miras Fatima, Moia Riccardo, Morawska Marta, Murru Roberta, Nath Uttam Kumar, Navarro-Bailón Almudena, Oliveira Ana C, Olivieri Jacopo, Oscier David, Panovska-Stavridis Irina, Papaioannou Maria, Papajík Tomas, Kubova Zuzana, Phumphukhieo Punyarat, Pierie Cheyenne, Puiggros Anna, Rani Lata, Reda Gianluigi, Rigolin Gian Matteo, Ruchlemer Rosa, Daniel de Deus Santos Marcos, Schipani Mattia, Schiwitza Annett, Shen Yandong, Simkovic Martin, Smirnova Svetlana, Abdelrahman Soliman Dina Sameh, Spacek Martin, Tadmor Tamar, Tomic Kristina, Tse Eric, Vassilakopoulos Theodoros, Visentin Andrea, Vitale Candida, von Tresckow Julia, Vrachiolias George, Vukovic Vojin, Walewska Renata, Wasik-Szczepanek Ewa, Xu Zhenshu, Yagci Munci, Yañez Lucrecia, Yassin Mohamed, Zuchnicka Jana, Angelopoulou Maria, Antic Darko, Biderman Bella, Catherwood Mark, Claus Rainer, Coscia Marta, Cuneo Antonio, Demirkan Fatih, Espinet Blanca, Gaidano Gianluca, Kalashnikova Olga B, Laurenti Luca, Nikitin Eugene, Pangalis Gerassimos A, Panagiotidis Panagiotis, Popov Viola Maria, Pospisilova Sarka, Sportoletti Paolo, Stavroyianni Niki, Tam Constantine, Trentin Livio, Chatzidimitriou Anastasia, Bosch Francesc, Doubek Michael, Ghia Paolo, Stamatopoulos Kostas
机构信息
Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece.
Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy.
出版信息
EClinicalMedicine. 2023 Nov 15;65:102307. doi: 10.1016/j.eclinm.2023.102307. eCollection 2023 Nov.
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.
背景
与普通人群相比，慢性淋巴细胞白血病（CLL）患者发生其他恶性肿瘤（OMs）的风险更高。然而，CLL相关危险因素和CLL导向治疗的影响仍不明确，这也是本研究的重点。
方法
我们进行了一项回顾性国际多中心研究，以评估19705例在2000年至2016年间被诊断为CLL、小淋巴细胞淋巴瘤或高计数CLL样单克隆B细胞淋巴细胞增多症患者的OMs发病率，并检测潜在危险因素。数据收集于2020年10月至2022年3月进行。
研究结果
在CLL诊断后的129254人年随访中，共诊断出3513例OMs（27.2例OMs/1000人年）。最常见的血液系统OMs是Richter转化、骨髓增生异常综合征（MDS）和急性髓系白血病（AML）。非黑色素瘤皮肤癌（NMSC）和前列腺癌是最常见的实体瘤（STs）。MDS和AML发生的唯一预测因素是使用氟达拉滨和环磷酰胺联合/不联合利妥昔单抗（FC±R）治疗（OR=3.7；95%CI=2.79-4.91；p<0.001）。STs在男性和免疫球蛋白重链可变基因未突变的患者中更常见（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导向治疗与非黑色素瘤皮肤癌和前列腺癌相关（OR=1.8；95%CI=1.3-2.41；p<0.001/OR=2.11；95%CI=1.12-3.97；p=0.021）。相比之下，未接受治疗的患者乳腺癌更常见（OR=0.17；95%CI=0.08-0.33；p<0.001）。患有CLL和OM的患者总生存期（OS）低于未患OM的患者。AML和MDS的OS最差（p<0.001）。
解读
CLL中的OMs影响OS。CLL治疗增加了AML/MDS、前列腺癌和NMSC的风险。FCR与AML/MDS风险增加相关。
资助
艾伯维公司，以及欧盟/欧洲制药工业协会联合会创新药物倡议联合事业协调项目HARMONY资助，项目编号116026 。
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