Pui Ching-Hon, Thiel Eckhard
St. Jude's Children's Research Hospital, Memphis, TN 38105, USA.
Semin Oncol. 2009 Aug;36(4 Suppl 2):S2-S16. doi: 10.1053/j.seminoncol.2009.05.002.
Acute lymphoblastic leukemia (ALL) 5-year survival rates are approaching 90% in children and 50% in adults who are receiving contemporary risk-directed treatment protocols. Current efforts focus not only on further improving cure rate but also on patient quality of life. Hence, all protocols decrease or limit the use of cranial irradiation as central nervous system (CNS)-directed therapy, even in patients with high-risk presenting features, such as the presence of leukemia cells in the cerebrospinal fluid (even resulting from traumatic lumbar puncture), adverse genetic features, T-cell immunophenotype, and a large leukemia cell burden. Current strategies for CNS-directed therapy involve effective systemic chemotherapy (eg, dexamethasone, high-dose methotrexate, intensive asparaginase) and early intensification and optimization of intrathecal therapy. Options under investigation for the treatment of relapsed or refractory CNS leukemia in ALL patients include thiotepa and intrathecal liposomal cytarabine. CNS involvement in non-Hodgkin lymphoma (NHL) is associated with young age, advanced stage, number of extranodal sites, elevated lactate dehydrogenase, and International Prognostic Index score. Refractory CNS lymphoma in patients with NHL carries a poor prognosis, with a median survival of 2 to 6 months; the most promising treatment, autologous stem cell transplant, can extend median survival from 10 to 26 months. CNS prophylaxis is required during the initial treatment of NHL subtypes that carry a high risk of CNS relapse, such as B-cell ALL, Burkitt lymphoma, and lymphoblastic lymphoma. The use of CNS prophylaxis in the treatment of diffuse large B-cell lymphoma is controversial because of the low risk of CNS relapse ( approximately 5%) in this population. In this article, we review current and past practice of intrathecal therapy in ALL and NHL and the risk models that aim to identify predictors of CNS relapse in NHL.
接受当代风险导向治疗方案的儿童急性淋巴细胞白血病（ALL）5年生存率接近90%，成人则为50%。当前的努力不仅集中在进一步提高治愈率，还关注患者的生活质量。因此，所有方案都减少或限制了作为中枢神经系统（CNS）导向治疗的颅脑照射的使用，即使是对于具有高危表现特征的患者，如脑脊液中存在白血病细胞（即使是由创伤性腰椎穿刺导致）、不良遗传特征、T细胞免疫表型以及较大的白血病细胞负荷。当前CNS导向治疗的策略包括有效的全身化疗（如地塞米松、大剂量甲氨蝶呤、强化门冬酰胺酶）以及鞘内治疗的早期强化和优化。正在研究的用于治疗ALL患者复发或难治性CNS白血病的选项包括噻替派和鞘内脂质体阿糖胞苷。非霍奇金淋巴瘤（NHL）的CNS受累与年轻、晚期、结外部位数量、乳酸脱氢酶升高以及国际预后指数评分相关。NHL患者的难治性CNS淋巴瘤预后较差，中位生存期为2至6个月；最有前景的治疗方法——自体干细胞移植，可将中位生存期从10个月延长至26个月。对于具有高CNS复发风险的NHL亚型，如B细胞ALL、伯基特淋巴瘤和淋巴母细胞淋巴瘤，在初始治疗期间需要进行CNS预防。由于弥漫性大B细胞淋巴瘤患者CNS复发风险较低（约5%），因此在其治疗中使用CNS预防存在争议。在本文中，我们回顾了ALL和NHL中鞘内治疗的当前和过去实践以及旨在识别NHL中CNS复发预测因素的风险模型。
