原发性中枢神经系统淋巴瘤的预后因素和治疗进展

Primary Central Nervous System Lymphoma (PCNSL): Prognosis Factors and Current Development in Treatment

原发性中枢神经系统淋巴瘤(PCNSL)是原发于脑和脊髓的非霍奇金氏淋巴瘤(NHL),临床上较罕见,仅占脑肿瘤的1%和结外NHL的1%～2%。近数十年来发病率逐渐上升。由于部位特殊,现有NHL的预后因素和治疗原则不适用于PCNSL。PCNSL发病率低,目前尚无标准的预后因素和一线标准治疗方案,但随着临床治疗经验的不断积累,在治疗上已取得一定的共识,使PCNSL中位生存期由早年单纯放疗的13～16个月增加到目前综合治疗的30～36个月,疗效有较明显提高。本文着重于评述近年来在免疫功能正常的PCNSL预后因素的确立和临床治疗方面取得的进展。目前PCNSL一般采用化疗和放疗联合的治疗措施,手术仅起到诊断作用。化疗在治疗PCNSL中不可缺少,但CHOP方案对PCNSL几乎无效。大剂量甲氨蝶呤(HD-MTX)是最有效的药物,大剂量阿糖胞苷(HD-Ara-C)是另一个常用的有效药物,鞘内给药有助于预防脑脊髓膜的肿瘤种植。PCNSL对放疗高度敏感,但单纯放疗复发率高,远期疗效差,放疗应在化疗完成后进行,多常用全颅加侵犯野放疗。为降低化放疗的远期神经毒性,有人尝试采用单纯化疗治疗PCNSL,对于获得完全缓解的患者放疗延迟至复发后再进行,远期疗效有待确定。自体造血干细胞移植支持下超大剂量化疗和抗CD20单克隆抗体也试用于治疗PCNSL,取得一定效果。目前全身HD-MTX、化疗后放疗的次序、年龄和PS是PCNSL最重要的预后因素。因此,采用含HD-MTX或/和HD-Ara-C等的联合化疗,同时鞘内注射MTX、Ara-C和地塞米松(DXM),结合颅脑放疗是现阶段治疗PCNSL最常用的治疗模式。

Primary central nervous system lymphoma (PCNSL) is a rare subtype of NHL confined to brain or spinal cord. PCNSL accounts for 1% of brain tumors and 1%-2% of extranodal lymphoma. The incidence of PCNSL steadily increases during the past decades. The international prognostic index (IPI) and standard treatment of systemic NHL are not suitable for PCNSL. Although there has still no established standard treatment or prognostic factors for PC-NSL, so consensus on therapeutic modality has been established based on accumulation of clinical experience. The medi-an survival of PCNSL patients has improved dramatically to 30-36 months by combination of chemotherapy and radiothera-py in recent years as compared with 13-16 months when radiotherapy was used alone. This review focused on the recent advances in identifying the prognostic factors and better clinical management of PCNSL in immuno-competent patients.The standard treatment for PCNSL so far is chemotherapy or chemotherapy combined with whole-brain radiotherapy.Surgery is mainly used for diagnosis. Chemotherapy is indispensable for the treatment of PCNSL, but CHOP regimen,which is standard for systemic NHL, failed to prolong the survival. High - dose methotrexate (HD-MTX) is the most effective drug and high dose AraC (HD-AraC) is the alternative. Furthermore, intrathecal administration of chemotherapeu- tic agents can reduce tumor seeding in the spinal cord and brain. PCNSL is highly sensitive to radiothera-py, but the recurrent rate is high and the survival time was short if used alone. Radiotherapy should be performed after the completion of chemotherapy in order to minimize the neurotoxicity. A new ap- proach is attempted to treat PCNSL with first-line chemotherapy alone and reserve radiotherapy for recurrence. High dose chemotherapy and anti-CD20 monoclonal antibody supported by autologous stem cell transplant has also been used with some success. Longer-term follow-up is needed to confirm the efficacy of these regimes. Systemic use of HD-MTX, age, performance status and sequential use of chemotherapy and radiotherapy are the most important prognostic fac-tors so far. We concluded that HD-MTX=/-HD-Ara-C containing regimen plus concurrent intrathecal chemothera-py (MTX, AraC and dexamethasone), combined with whole brain irradiation is the current therapeutic model for PC-NSL.