Doolittle Nancy D, Jahnke Kristoph, Belanger Richard, Ryan Deborah A, Nance Robert W, Lacy Cynthia A, Tyson Rose Marie, Haluska Marianne, Hedrick Nancy A, Varallyay Csanad, Neuwelt Edward A
Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA.
Leuk Lymphoma. 2007 Sep;48(9):1712-20. doi: 10.1080/10428190701493902.
Five patients with relapsed PCNSL were given chemo-immunotherapy (rituximab followed by carboplatin and methotrexate) with osmotic blood-brain barrier (BBB) opening. Four patients achieved CR and one patient had stable disease. Two patients (2/5) had durable responses (survival: 230+, 122+, 82, 42, 38 weeks). One patient later received Indium-111-ibritumomab tiuxetan and Yttrium-90-ibritumomab tiuxetan intravenous, without BBB opening. There was good uptake of Indium-111 ibritumomab tiuxetan in tumor on SPECT scan after 48 h. Estimated radiation doses to brain around and distant from tumor were within safe limits. After Ytrium-90 ibritumomab tiuxetan there was CR in enhancing tumor where the BBB was leaky, but lesions occurred in other brain regions, where the BBB was intact during Yttrium-90 ibritumomab tiuxetan infusion. Imaging and dosimetry with Indium-111 ibritumomab tiuxetan and efficacy with Yttrium-90 ibritumomab tiuxetan suggest the need for future enhanced CNS delivery when using monoclonal or radiolabeled antibodies, as intravenous delivery alone may provide modest clinical benefit due to limited BBB permeability.
5例复发性原发性中枢神经系统淋巴瘤患者接受了化疗免疫治疗（利妥昔单抗后联合卡铂和甲氨蝶呤），同时进行渗透性血脑屏障（BBB）开放。4例患者达到完全缓解（CR），1例患者病情稳定。2例患者（2/5）有持久反应（生存期：230+、122+、82、42、38周）。1例患者后来接受了静脉注射铟-111-替伊莫单抗和钇-90-替伊莫单抗，未进行血脑屏障开放。48小时后SPECT扫描显示肿瘤对铟-111替伊莫单抗摄取良好。肿瘤周围及远处脑组织的估计辐射剂量在安全范围内。钇-90替伊莫单抗治疗后，血脑屏障渗漏的强化肿瘤区域出现完全缓解，但在钇-90替伊莫单抗输注期间血脑屏障完整的其他脑区出现病变。铟-111替伊莫单抗的成像和剂量测定以及钇-90替伊莫单抗的疗效表明，在使用单克隆或放射性标记抗体时，未来需要增强中枢神经系统给药，因为由于血脑屏障通透性有限，单纯静脉给药可能仅提供适度的临床益处。
