Chamberlain M C, Kormanik P, Glantz M
University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-8421, USA.
Oncol Rep. 1998 Mar-Apr;5(2):521-5. doi: 10.3892/or.5.2.521.
Primary central nervous system lymphomas (PCNSL) are chemosensitive primary brain tumors and are treated primarily with adjuvant chemotherapy. Nonetheless, therapy is palliative with the majority of tumors recurring in brain parenchyma. A common pattern of PCNSL recurrence is that of cerebrospinal fluid (CSF) dissemination manifested as lymphomatous meningitis (LM). Fourteen patients (8 men; 6 women) 34-76 years of age (median 56 years) with recurrent PCNSL manifested as either lymphomatous meningitis (8 patients) or combined parenchymal and CSF disseminated tumor (5) were retrospectively evaluated. All patients had received prior adjuvant therapy including surgery (gross total resection in 3; biopsy in 11), radiotherapy (whole brain in 11; craniospinal in 1; and orbital in 1) and chemotherapy (systemic in 13; intraventricular in 4). At recurrence, documented by either positive CSF cytology (14 patients) or neuroradiographic evidence of disease progression (6 patients), all patients were evaluated for extent of central nervous system disease. Two patients not previously irradiated were treated with whole brain radiotherapy. Eight patients received systemic chemotherapy including 7 patients (Brown University; Group A) treated with either high dose methotrexate (n=4) or cytosine arabinoside (n=3). Seven patients (UCSD: Group B) received intraventricular chemotherapy (methotrexate 5; cytosine arabinoside 4; thio-TEPA 4) without concomitant high dose systemic chemotherapy. Four of 14 patients (28.6%) are disease-free and have durable responses (median 36 months, range 22-56 months). Ten patients (71.4%) have died of disease progression (5 due to combined PCNSL and LM; 4 due to LM; and 1 due to PCNSL). Median survival was 5.5 months with a range of 3-12 months. Grade III/IV myelosuppression was seen in 5 patients, all as a result of systemic chemotherapy (Group A patients). Aseptic meningitis due to intraventricular chemotherapy was seen in 7 patients (Group B patients). No treatment-related deaths occurred. Four patients are disease-free and manifest leukoencephalopathy of whom 2 are symptomatic. Outcome was comparable in Group A and B patients. Recurrent PCNSL complicated by LM may be palliated by combined modality therapy and in this small series, approximately one-quarter of patients (two from each treatment group) are long-term survivors and disease-free. Outcome is similar in patients treated with intraventricular chemotherapy as compared to patients treated with high dose systemic methotrexate or cytosine arabinoside. Treatment-related toxicity was manageable however delayed neurotoxicity is seen in disease-free survivors.
原发性中枢神经系统淋巴瘤（PCNSL）是对化疗敏感的原发性脑肿瘤，主要采用辅助化疗进行治疗。尽管如此，治疗仍为姑息性的，大多数肿瘤会在脑实质复发。PCNSL复发的一种常见模式是脑脊液（CSF）播散，表现为淋巴瘤性脑膜炎（LM）。对14例年龄在34 - 76岁（中位年龄56岁）的复发性PCNSL患者（8例男性；6例女性）进行了回顾性评估，这些患者表现为淋巴瘤性脑膜炎（8例）或合并脑实质和CSF播散性肿瘤（5例）。所有患者均接受过先前的辅助治疗，包括手术（3例全切除；11例活检）、放疗（11例全脑放疗；1例全脑脊髓放疗；1例眼眶放疗）和化疗（13例全身化疗；4例脑室内化疗）。复发时，通过CSF细胞学阳性（14例患者）或神经影像学疾病进展证据（6例患者）得以证实。所有患者均评估了中枢神经系统疾病的范围。2例先前未接受过放疗的患者接受了全脑放疗。8例患者接受了全身化疗，其中7例（布朗大学；A组）接受了高剂量甲氨蝶呤（n = 4）或阿糖胞苷（n = 3）治疗。7例（加州大学圣地亚哥分校；B组）患者接受了脑室内化疗（甲氨蝶呤5例；阿糖胞苷4例；硫替派4例），未同时进行高剂量全身化疗。14例患者中有4例（28.6%）无疾病进展且有持久反应（中位时间36个月，范围22 - 56个月）。10例患者（71.4%）死于疾病进展（5例死于合并PCNSL和LM；4例死于LM；1例死于PCNSL）。中位生存期为5.5个月，范围为3 - 12个月。5例患者出现III/IV级骨髓抑制，均为全身化疗（A组患者）所致。7例患者（B组患者）出现了因脑室内化疗导致的无菌性脑膜炎。未发生与治疗相关的死亡。4例无疾病进展的患者出现了白质脑病，其中2例有症状。A组和B组患者的结果相当。合并LM的复发性PCNSL可通过综合治疗得到缓解，在这个小系列研究中，约四分之一的患者（每个治疗组各2例）为长期存活且无疾病进展。与接受高剂量全身甲氨蝶呤或阿糖胞苷治疗的患者相比，接受脑室内化疗的患者结果相似。治疗相关毒性是可控的，然而在无疾病进展的幸存者中可见延迟性神经毒性。
