Oubari Sara, Papathanasiou Maria, Michel Lars, Rassaf Tienush, Thimm Andreas, Hagenacker Tim, Ehling Daniela, Wieczorek Stefan, Naser Eyad, Hegenbart Ute, Schönland Stefan, Dührsen Ulrich, Reinhardt Hans Christian, Carpinteiro Alexander
Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, Essen, 45147, Germany.
Interdisciplinary Amyloidosis Network, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Ann Hematol. 2025 Mar;104(3):1777-1788. doi: 10.1007/s00277-025-06256-7. Epub 2025 Mar 22.
Systemic light-chain amyloidosis (AL) is an acquired protein misfolding disease characterized by deposition of immunoglobulin light-chain fibrils most often secreted from clonal plasma cells. In this retrospective study we analyzed the impact of iFISH aberrations on clinical characteristics and outcomes in 175 AL patients presented between 2015 and 2024. The most common aberrations were t(11;14) (57%), deletion 13q14 (33%), +1q21 (21%), hyperdiploidy (21%) and deletion 16q23 (17%). Significant elevations in dFLC levels were observed in patients with + 1q21 (median 407 vs. 213 mg/l, p = 0.04) and deletion 16q23 (median 476 vs. 204, p = 0.006). Only + 1q21 was associated with increased levels of cardiac biomarkers NTproBNP (median 9945 vs. 3538 pg/ml, p = 0.002) and hsTnT (median 110 vs. 53 ng/l, p = 0.002). This resulted in an increased proportion of patients with Mayo stage IIIb (53% vs. 26%, p = 0.01). Patients with + 1q21 had more advanced plasma cell disease (p = 0.0004). Our study highlights for the first time + 1q21 as the key aberration associated with advanced cardiac and plasma cell disease. After 17 months of follow-up, overall survival was significantly worse in patients with + 1q21 treated with daratumumab (7.2 months vs. not reached, p = 0.006). Alternative therapeutic approaches such as CAR-T therapies or bispecific antibodies should be further investigated.
系统性轻链淀粉样变性（AL）是一种获得性蛋白质错误折叠疾病，其特征是免疫球蛋白轻链原纤维沉积，这些原纤维大多由克隆性浆细胞分泌。在这项回顾性研究中，我们分析了间期荧光原位杂交（iFISH）异常对2015年至2024年间就诊的175例AL患者临床特征和预后的影响。最常见的异常为t(11;14)（57%）、13q14缺失（33%）、+1q21（21%）、超二倍体（21%）和16q23缺失（17%）。+1q21和16q23缺失的患者血清游离轻链（dFLC）水平显著升高（+1q21患者中位数为407 vs. 213 mg/l，p = 0.04；16q23缺失患者中位数为476 vs. 204，p = 0.006）。只有+1q21与心脏生物标志物N末端B型利钠肽原（NTproBNP）水平升高相关（中位数为9945 vs. 3538 pg/ml，p = 0.002）以及高敏肌钙蛋白T（hsTnT）水平升高相关（中位数为110 vs. 53 ng/l，p = 0.002）。这导致梅奥IIIb期患者比例增加（53% vs. 26%，p = 0.01）。+1q21的患者浆细胞疾病更严重（p = 0.0004）。我们的研究首次强调+1q21是与晚期心脏和浆细胞疾病相关的关键异常。在17个月的随访后，接受达雷妥尤单抗治疗的+1q21患者总生存期显著更差（7.2个月 vs. 未达到，p = 0.006）。应进一步研究如嵌合抗原受体T细胞（CAR-T）疗法或双特异性抗体等替代治疗方法。
