Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
Center for International Blood and Marrow Transplantation and Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin.
Biol Blood Marrow Transplant. 2018 Mar;24(3):581-586. doi: 10.1016/j.bbmt.2017.10.015. Epub 2017 Oct 12.
Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the only known curative treatment for CLL. The potential benefit of transplantation is most likely due to the presence of alloreactive donor T cells that mediate the graft-versus-leukemia (GVL) effect. The recognition of potentially tumor-specific antigens in the context of class I and II major histocompatibility complex on malignant B lymphocytes by donor T cells may be influenced by subtle differences in the highly polymorphic HLA locus. Given previous reports of specific HLA alleles impacting the incidence of CLL and the clinical outcomes of allo-HCT for CLL, we sought to study the overall survival and progression-free survival of a large cohort of patients with CLL who underwent allo-HCT from fully HLA-matched related and unrelated donors at Center for International Blood and Marrow Transplant Research transplantation centers. We found no statistically significant association of allo-HCT outcomes in CLL based on previously reported HLA combinations. Additional study is needed to further define the immunologic features that portend a more favorable GVL effect after allo-HCT for CLL.
慢性淋巴细胞白血病(CLL)是一种常见的血液系统恶性肿瘤,有许多非常有效的治疗方法。化疗耐药疾病,通常表现为 17p 染色体缺失,历史上与非常差的预后相关,导致适合医学条件的患者接受异基因造血干细胞移植(allo-HCT)。尽管随着新型靶向治疗 CLL 的出现,allo-HCT 的应用有所减少,但人们仍然非常关注可能影响 allo-HCT 疗效的因素,allo-HCT 是 CLL 唯一已知的治愈性治疗方法。移植的潜在益处可能归因于存在同种异体反应性供体细胞 T 细胞,这些细胞介导移植物抗白血病(GVL)效应。供体细胞 T 细胞在恶性 B 淋巴细胞的 I 类和 II 类主要组织相容性复合物背景下识别潜在的肿瘤特异性抗原,可能受到 HLA 基因座高度多态性的细微差异的影响。鉴于先前有报道称特定 HLA 等位基因影响 CLL 的发病率和 CLL allo-HCT 的临床结局,我们试图研究在国际血液和骨髓移植研究中心,来自完全 HLA 匹配的相关和无关供体的大量 CLL 患者接受 allo-HCT 的总生存率和无进展生存率。我们没有发现基于先前报道的 HLA 组合的 CLL allo-HCT 结果存在统计学显著关联。需要进一步研究以进一步确定免疫特征,这些特征预示着 CLL allo-HCT 后更有利的 GVL 效应。