Effects of addition of rituximab to chemotherapy on central nervous system events in patients with diffuse large B-cell lymphoma
Effects of addition of rituximab to chemotherapy on central nervous system events in patients with diffuse large B-cell lymphoma
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DOI：
10.3892/mco.2015.546
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发表时间：
2015-07-01
影响因子：
1.2
通讯作者：
Yip, Sze Fai
中科院分区：
文献类型：
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作者：
Law, Man Fai;Chan, Hay Nun;Yip, Sze Fai
本研究的目的是评估在化疗中加入利妥昔单抗是否能减少中枢神经系统（CNS）事件，并确定与中枢神经系统受损伤相关的危险因素。1995年1月至2012年12月期间诊断为弥漫性大b细胞淋巴瘤（DLBCL）的患者，既往无中枢神经系统疾病，纳入本研究。患者接受环磷酰胺、阿霉素、长春新碱和强的松龙（CHOP）化疗或CHOP联合利妥昔单抗（R-CHOP）化疗，均有治愈目的。比较两组后续中枢神经系统事件的发生率。共招募110例患者，其中45例（41%）接受CHOP， 65例（59%）接受R-CHOP。12例患者（10.9%）随后表现出中枢神经系统受累。从最初的DLBCL诊断到中枢神经系统疾病的中位时间为6.7个月（范围1.3-23.8个月）。CHOP组中枢神经系统疾病发生率为15.5% (7/45)，R-CHOP组为7.6%（5/65）。CHOP组预计3年中枢神经系统疾病发生率为18%，而R-CHOP组为9% （P=0.15）。中枢神经系统疾病患者的生存期较差，中位生存期为5.8个月。在Cox比例模型的多变量分析中，IV期疾病仍然是CNS疾病的独立预测因子（风险比= 7.75,95%置信区间：1.67-35.92，P=0.009）。总之，在我们的研究中，化疗中加入利妥昔单抗似乎并没有降低中枢神经系统事件的风险。需要其他有效的预防措施来减少中枢神经系统事件的发生率。高剂量静脉注射甲氨蝶呤可穿过血脑屏障，可用于高危患者的中枢神经系统预防。
The aim of this study was to evaluate whether the addition of rituximab to chemotherapy reduces central nervous system (CNS) events and to identify the risk factors associated with CNS involvement. Patients who were diagnosed with diffuse large B-cell lymphoma (DLBCL) between January, 1995 and December, 2012, without prior CNS disease, were recruited in this study. The patients received chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or CHOP with rituximab (R-CHOP), with curative intent. The incidence rate of subsequent CNS events was compared between the two groups. A total of 110 patients were recruited, 45 (41%) of whom received CHOP and 65 (59%) R-CHOP. A total of 12 patients (10.9%) subsequently exhibited CNS involvement. The median time from the initial DLBCL diagnosis to CNS disease was 6.7 months (range, 1.3-23.8 months). The CNS disease rate was 15.5% (7/45) in the CHOP group vs. 7.6% (5/65) in the R-CHOP group. The projected 3-year CNS disease rate was 18% in the CHOP group vs. 9% in the R-CHOP group (P=0.15). The survival of patients with CNS disease was poor, with a median survival of 5.8 months. On multivariate analysis using the Cox proportional model, stage IV disease remained an independent predictor of CNS disease (hazard ratio = 7.75, 95% confidence interval: 1.67-35.92, P=0.009). In conclusion, the addition of rituximab to chemotherapy did not appear to reduce the risk of CNS events in our study. Other effective prophylactic measures are required to reduce the incidence of CNS events. High-dose intravenous methotrexate crosses the blood-brain barrier and may be used as CNS prophylaxis in high-risk patients.