G-PCNSL-SG1 研究中脑膜播散转移对原发中枢神经系统淋巴瘤的转归的影响

2011年lugano国际淋巴瘤会议（icml） 关注中枢神经淋巴瘤篇 摘要031

中国肿瘤化疗 译  发布日期：17:50 2011-9-13武汉协和医院肿瘤中心刘红利

研究背景：脑膜播散转移对原发中枢神经系统淋巴瘤的生存预后的影响仍然存在争议。本研究对一项多中心随机对照试验（g-pcnsl-sg1）中出现的脑膜播散对病人的转归影响进行了分析。

方法：入组成年的免疫功能正常病例，治疗初期均给予最多6程的大剂量甲氨蝶呤（mtx; 4g/m2)为基础的化疗，不予鞘内注射治疗。随机分入放疗组的病例随后接受每次1.5gy，共45gy的全脑放疗（wbrt）；随机分入化疗组的病例在获得完全缓解后不再接受进一步的治疗，如未获得完全缓解则需接受大剂量阿糖胞苷化疗。脑膜播散转移的定义是采用以下至少一种检测方法在脑脊液中检测到淋巴瘤细胞：细胞形态学、重组免疫球蛋白重链基因聚合酶链反应（igh-pcr）的方法检测到克隆b细胞或 mri显示软脑膜对比增强。

结果：所有符合入组标准的526例患者均被纳入分析。初诊时发现有脑膜播散转移的患者共有104例：95例细胞形态学诊断，16例pcr诊断，17例mri诊断。脑膜转移病例和无脑膜转移病例的包括年龄、kps评分、性别、血清乳酸脱氢酶、淋巴瘤部位、活检方式、组织学、脑脊液蛋白水平(>45mg/dl) 和眼眶受侵情况的治疗前临床特征没有明显差别（所有p>0.05）。但脑膜转移病例的脑脊液淋巴细胞增多(>5/ll)发生率显著增加（37 vs . 14%，p<0.001）。脑膜转移组和无脑膜转移组采用的化疗方案(大剂量mtx: 83 vs. 75%, 大剂量mtx联合异环磷酰胺: 17 vs. 25%)和全脑放疗情况(39 vs. 34%)无明显区别。脑膜转移组的中位总生存时间（oas）为21.5个月（95% ci：17.1-25.8), 无脑膜转移组为22.4个月（17.3-27.5)（p=0.8）；两组的中位无进展生存时间(pfs）分别为6.1个月（1.6-10.5）和7.0个月（5.2-8.8）（p=0.9）。与脑脊液正常病例相比，脑脊液蛋白水平升高或脑脊液淋巴细胞增多病例的中位oas和pfs无显著差异。

结论：脑膜播散转移与脑脊液蛋白水平升高和脑脊液淋巴细胞增多对本研究的生存结果无影响。

 

‘‘focus on. . .’’ session: primary cns lymphoma

031 impact of meningeal dissemination (md) on outcome in primary cns lymphoma in the g-pcnsl-sg1 trial

background: the prognostic impact of md in pcnsl is still debated. within the framework of a multicenter randomized trial (g-pcnsl-sg1) we evaluated patients for outcome according to the presence of md.

methods: immunocompetent adult patients were initially treated with up to six cycles of high-dose methotrexate (hd-mtx; 4g/m2) based chemotherapy without intrathecal therapy. those randomized to radiotherapy subsequently received whole-brain radiotherapy (wbrt) with 45 gy, in 1.5 gy fractions; those randomized to chemotherapy did not receive further therapy in case of complete remission or highdose cytarabine when complete response was not achieved. md was defined by the presence of lymphoma cells in the cerebrospinal fluid (csf) detected by at least one of
the following methods: cytomorphology, detection of clonal b cells by polymerase chain reaction of rearranged immunoglobulin heavy-chain genes (igh-pcr) or contrast enhancement of the leptomeninges on mri.

results: all 526 patients fulfilling the eligibility criteria were entered into the analysis. md at presentation was detected in 104 (19.8 %) patients: 95 by cytomorphology, 16 by pcr and 17 by mri. pretherapeutic characteristics including age, karnofsky performance score, sex, serum lactate dehydrogenase, lymphoma localization, mode of biopsy, histology, csf protein elevation (>45mg/dl) and ocular involvement did not significantly differ in patients with md and other patients (all p>0.05). only csf pleocytosis (>5/ll) was significantly more frequent in patients with md (37 vs. 14%,
p<0.001). the type of chemotherapy (hd-mtx: 83 vs. 75%, hd-mtx and ifosfamide: 17 vs. 25%) applied and the frequency of wbrt (39 vs. 34%) were not significantly different in the group with and without md. median overall survival (oas) in the md group was 21.5 (95% ci 17.1-25.8) months as compared to 22.4 (17.3-27.5) months in other patients (p=0.8); median progression free survival (pfs) was 6.1 (1.6-10.5) and 7.0 (5.2-8.8) months, respectively (p=0.9). median oas and pfs were not significantly different in patients with elevated csf protein or csf pleocytosis compared to patients with normal csf values.

conclusion: md, elevated csf protein and csf pleocytosis had no impact on outcome in this trial.