Haematology Department, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Intern Med J. 2012 Oct;42(10):1113-9. doi: 10.1111/j.1445-5994.2011.02587.x.
Recent reports suggest genetic polymorphisms influence susceptibility to rituximab-induced late-onset neutropenia (LON), which in turn may be a predictor of good outcome in B-cell lymphoma.
We report the largest study to date assessing FCGR3A-V158F polymorphisms in diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide/hydroxydaunorubicin/Oncovin (vincristine)/prednisone/rituximab (CHOP-R). The influence of C1qA-A276G polymorphisms in DLBCL, and the impact of both polymorphisms on susceptibility to LON and outcome were also examined.
115 DLBCL patients treated with CHOP-R were compared with 105 healthy White people controls with regards to FCGR3A-V158F and C1qA-A276G polymorphisms. LON incidence and event-free and overall survival (EFS and OS) were analysed for linkage to either polymorphism.
The FCGR3A-V158F but not the C1qA-A276G polymorphism influenced the risk of developing LON. 50% of FCGR3A-158V/V patients experienced LON. In contrast, only 7% V/F and 2% F/F experienced LON. The FCGR3A-158V/V genotype was associated with LON compared with V/F (P = 0.028) and F/F genotypes (P = 0.005). Although no patients with either LON or FCGR3A-158V homozygosity relapsed compared with 33% FCGR3A-158F/F and 21% non-LON, this did not translate into improved EFS or OS.
Polymorphic analysis may be a predictive tool to identify those at high risk of LON. Prospective studies are required to establish definitively if LON or FCGR3A-158V/V genotype influences outcome.
最近的报告表明，遗传多态性影响利妥昔单抗诱导的迟发性中性粒细胞减少症（LON）的易感性，而 LON 反过来又可能是 B 细胞淋巴瘤良好预后的预测因子。
我们报告了迄今为止评估接受环磷酰胺/阿霉素/长春新碱/泼尼松/利妥昔单抗（CHOP-R）治疗的弥漫性大 B 细胞淋巴瘤（DLBCL）中 FCGR3A-V158F 多态性的最大研究。还检查了 C1qA-A276G 多态性在 DLBCL 中的影响，以及这两种多态性对 LON 易感性和结果的影响。
将 115 例接受 CHOP-R 治疗的 DLBCL 患者与 105 例健康白种人对照者进行比较，比较 FCGR3A-V158F 和 C1qA-A276G 多态性。分析 LON 发生率和无事件生存（EFS）和总生存（OS）与两种多态性的关联。
FCGR3A-V158F 但不是 C1qA-A276G 多态性影响 LON 发生的风险。50%的 FCGR3A-158V/V 患者发生 LON。相比之下，V/F 患者只有 7%和 F/F 患者只有 2%发生 LON。与 V/F（P=0.028）和 F/F 基因型（P=0.005）相比，FCGR3A-158V/V 基因型与 LON 相关。尽管没有 LON 或 FCGR3A-158V 纯合子的患者复发，而 FCGR3A-158F/F 和非 LON 患者的复发率分别为 33%和 21%，但这并未转化为 EFS 或 OS 的改善。
多态性分析可能是识别 LON 高危患者的预测工具。需要前瞻性研究来确定 LON 或 FCGR3A-158V/V 基因型是否影响结果。
