New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma: a retrospective study.
New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma: a retrospective study.
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弥漫性大B细胞淋巴瘤中枢神经系统复发的新危险因素和新趋势：回顾性研究
DOI：
10.1186/s40880-016-0150-y
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发表时间：
2016-09-13
影响因子：
--
通讯作者：
Xia ZJ
中科院分区：
文献类型：
--
作者：
Cai QQ;Hu LY;Geng QR;Chen J;Lu ZH;Rao HL;Liu Q;Jiang WQ;Huang HQ;Lin TY;Xia ZJ
背景：在弥漫性大B细胞淋巴瘤(DLBCL)患者中，中枢神经系统(CNS)复发并不常见，但几乎总是致命的。本研究旨在探讨DLBCL患者中枢神经系统复发的危险因素，评价利妥昔单抗联合鞘内化疗减少中枢神经系统复发的疗效。方法：选择2003-01/2012-12中山大学肿瘤防治中心收治的511例DLBCL患者。在这些患者中，376例接受R-CHOP方案(利妥昔单抗、环磷酰胺、阿霉素、长春新碱和强的松)作为主要治疗方案，135例接受CHOP方案(环磷酰胺、阿霉素、长春新碱和强的松)作为主要治疗方案。对于那些被认为是中枢神经系统复发的高危人群，给予鞘内化疗预防(甲氨蝶呤加阿糖胞苷)。在整个队列中，特别是在R-CHOP集合中，单因素分析采用Kaplan-Meier方法，多因素分析采用Cox比例风险模型。结果：在中位数46个月的随访中，25例(4.9%)患者出现了中枢神经系统复发。利妥昔单抗治疗后中枢神经系统复发有减少的趋势，3年累计复发率CHOP组为7.1%，R-CHOP组为2.7%(P=0.045)。鞘内化疗预防在预防中枢神经系统复发方面没有太大益处。骨骼受累[危险比(HR)=4.21，95%可信区间(CI)1.38~12.77]，肾脏受累(HR=3.85，95%可信区间1.05~14.19)，碱性磷酸酶(ALP)、谷草转氨酶(GT)110U/L(HR=3.59，95%可信区间1.25~10.34)，血清白蛋白(ALB)及Lt；在整个队列中，35g/L(HR=3.63，95%CI 1.25~10.51)、利妥昔单抗治疗(HR=0.34，95%CI 0.12~0.96)、完全缓解时间(HR=0.22，95%CI 0.06~0.78)是CNS复发的独立预测因素。骨骼受累(HR=4.44，95%CI 1.08~18.35)、骨髓受累(HR=11.70，95%CI 2.24~60.99)和肾脏受累(HR=10.83，95%CI 2.27~51.65)是R-CHOP组中枢神经系统复发的独立危险因素。结论：在本研究中，利妥昔单抗可降低DLBCL的中枢神经系统复发率，而单纯鞘内化疗预防并不足以预防CNS复发。血清ALB、ALP水平和完全缓解时间是DLBCL患者中枢神经系统复发的新的独立预测因素。在接受R-CHOP方案的患者中，发现中枢神经系统复发增加的趋势与结外病变有关。
Background:In patients with diffuse large B-cell lymphoma (DLBCL), central nervous system (CNS) relapse is uncommon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the efficacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction.Methods:A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat-sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathecal chemotherapy prophylaxis (methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R-CHOP set in particular, the Kaplan-Meier method coupled with the log-rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Differences were evaluated using a two-tailed test, and P < 0.05 was considered significant.Results:At a median follow-up of 46 months, 25 (4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3-year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R-CHOP group (P = 0.045). Intrathecal chemotherapy prophylaxis did not confer much benefit in terms of preventing CNS relapse. Bone involvement [hazard ratio (HR) = 4.21, 95% confidence interval (CI) 1.38-12.77], renal involvement (HR = 3.85, 95% CI 1.05-14.19), alkaline phosphatase (ALP) >110 U/L (HR = 3.59, 95% CI 1.25-10.34), serum albumin (ALB) <35 g/L (HR = 3.63, 95% CI 1.25-10.51), treatment with rituximab (HR = 0.34, 95% CI 0.12-0.96), and a time to complete remission ≤ 108 days (HR = 0.22, 95% CI 0.06-0.78) were independent predictive factors for CNS relapse in the entire cohort. Bone involvement (HR = 4.44, 95% CI 1.08-18.35), bone marrow involvement (HR = 11.70, 95% CI 2.24-60.99), and renal involvement (HR = 10.83, 95% CI 2.27-51.65) were independent risk factors for CNS relapse in the R-CHOP set.Conclusions:In the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemotherapy prophylaxis alone was not sufficient for preventing CNS relapse. Serum levels of ALB and ALP, and the time to complete remission were new independent predictive factors for CNS relapse in the patients with DLBCL. In the patients received R-CHOP regimen, a trend of increased CNS relapse was found to be associated with extranodal lesions.
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影响因子：
2.1
作者：
Shimazu, Yutaka;Notohara, Kenji;Ueda, Yasunori
通讯作者：
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影响因子：
51.1
作者：
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作者：
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通讯作者：
Cai QQ
影响因子：
12.8
作者：
Park, Byeong-Bae;Kim, Jong Gwang;Kim, Won Seog
通讯作者：
Kim, Won Seog