肿瘤细胞治疗研究
英文原题：Richter Transformation in Chronic Lymphocytic Leukemia: Current Treatment Challenges and Evolving Therapies.
Richter 转化（RT）发生于 2-10% 的慢性淋巴细胞白血病（CLL）患者，可演变为侵袭性淋巴瘤——最常见为弥漫大 B 细胞淋巴瘤——预后较差，尤其当与 CLL 克隆相关时。
Richter转化（RT）影响2%–10%的慢性淋巴细胞白血病（CLL）患者，可进展为侵袭性淋巴瘤，最常见为弥漫大B细胞淋巴瘤；若与CLL具有克隆相关性，预后尤其不佳。关键风险因素包括IGHV未突变、TP53和NOTCH1突变、具有典型模式的B细胞受体及复杂细胞遗传学。本综述总结RT生物学、临床预测因素和治疗结局。传统免疫化疗（如R-CHOP）的完全缓解率约为20%–30%，中位总生存期为6–12个月；强化方案（R-EPOCH、hyper-CVAD）仅带来有限改善。异基因造血干细胞移植可能治愈，但由于治疗相关死亡率高，仅适用于身体状况良好的患者。新兴疗法包括布鲁顿酪氨酸激酶和BCL-2抑制剂，可产生部分缓解，但无进展生存期较短。靶向CD19的CAR-T 细胞疗法总缓解率为60%–65%，但复发仍常见。双特异性抗体（如CD3×CD20药物epcoritamab和mosunetuzumab）治疗复发/难治性RT显示出有前景活性，且毒性可耐受。正在开展的试验探索与免疫检查点抑制剂联合、三药方案，以及ROR1、CD47和CDK9等新靶点。持续研究优化诱导和巩固治疗以及创新免疫疗法，对于改善这种生物学特征独特、高危的CLL相关淋巴瘤结局至关重要。
Richter transformation (RT) affects 2-10% of chronic lymphocytic leukemia (CLL) patients, evolving into an aggressive lymphoma-most often diffuse large B-cell lymphoma-with poor prognosis, especially when clonally related to CLL. Key risk factors include unmutated IGHV, TP53 and NOTCH 1 mutations, stereotyped B-cell receptors, and complex cytogenetics. This review summarizes RT biology, clinical predictors, and treatment outcomes. Traditional chemoimmunotherapy (e.g., R-CHOP) yields complete response rates around 20-30% and median overall survival of 6-12 months; intensified regimens (R-EPOCH, hyper-CVAD) offer only modest gains. Allogeneic hematopoietic stem cell transplantation is potentially curative but limited to fit patients due to high treatment-related mortality. Emerging therapies now include Bruton's tyrosine kinase and BCL-2 inhibitors, which achieve partial responses but short progression-free survival. CD19-directed chimeric antigen receptor T-cell therapies produce overall response rates of 60-65%, though relapses remain frequent. Bispecific antibodies (e.g., CD3 CD20 agents epcoritamab and mosunetuzumab) show promising activity and tolerable toxicity in relapsed/refractory RT. Ongoing trials are exploring combinations with checkpoint inhibitors, triplet regimens, and novel targets such as ROR1, CD47, and CDK9. Continued research into optimized induction, consolidation, and innovative immunotherapies is essential to improve outcomes in this biologically distinct, high-risk CLL-related lymphoma.
MEMBER ACCOUNT
登录成功会直接打开下一页。
