Fisher Paul G, Kadan-Lottick Nina S, Korones David N
Department of Neurology, Stanford University School of Medicine, Palo Alto, California 94305-5235, USA.
J Pediatr Hematol Oncol. 2002 May;24(4):274-8. doi: 10.1097/00043426-200205000-00011.
Intrathecal thiotepa is recommended as a treatment of leptomeningeal metastases (LM) in children, although published data to support this approach are limited. The authors sought to determine the efficacy of intrathecal thiotepa for pediatric LM.
The authors reviewed all children treated with intrathecal thiotepa for LM at two tertiary children's hospitals, assessing outcome by cerebrospinal fluid cytology, neuroimaging, neurologic examination, and overall survival rate.
Fifteen children with LM evidenced by malignant cells in the cerebrospinal fluid (mean age 7.3 years; five medulloblastoma, one anaplastic astrocytoma, one glioblastoma, one retinoblastoma, one neuroblastoma, two rhabdomyosarcoma, one non-Hodgkin lymphoma, two acute lymphoblastic leukemia, and one acute myelogenous leukemia) were treated with intrathecal thiotepa at 5 to 11.5 mg/m2 per dose for two to seven doses. Five children received concomitant craniospinal irradiation; 12 received simultaneous systemic or other intrathecal chemotherapy, or both. Four children experienced clearance of malignant cells from the spinal fluid, but this response was sustained in only two. All four children with cytologic response received concurrent radiotherapy, chemotherapy, or both. No patients showed partial or complete response on neuroimaging. Only one child had improvement on the neurologic examination; six were unchanged and eight had worsening neurologic signs. Median survival was 15.1 weeks, with a 1-year overall survival rate of 26.7% (standard error 11.4%).
The unfavorable outcomes observed suggest that intrathecal thiotepa adds little to combination therapy for pediatric LM.
鞘内注射噻替派被推荐用于治疗儿童软脑膜转移瘤（LM），尽管支持这种治疗方法的已发表数据有限。作者试图确定鞘内注射噻替派治疗儿童LM的疗效。
作者回顾了两家三级儿童医院所有接受鞘内注射噻替派治疗LM的儿童，通过脑脊液细胞学检查、神经影像学检查、神经系统检查和总生存率评估治疗结果。
15例脑脊液中出现恶性细胞证实为LM的儿童（平均年龄7.3岁；5例髓母细胞瘤、1例间变性星形细胞瘤、1例胶质母细胞瘤、1例视网膜母细胞瘤、1例神经母细胞瘤、2例横纹肌肉瘤、1例非霍奇金淋巴瘤、2例急性淋巴细胞白血病和1例急性髓细胞白血病）接受了鞘内注射噻替派治疗，剂量为每平方米5至11.5毫克，共注射2至7次。5名儿童同时接受了全脑全脊髓放疗；12名儿童同时接受了全身化疗或其他鞘内化疗，或两者同时进行。4名儿童脑脊液中的恶性细胞消失，但只有2名儿童的这种反应得以持续。所有4例有细胞学反应的儿童均接受了同步放疗、化疗或两者同时进行。没有患者在神经影像学检查中显示部分或完全缓解。只有1名儿童的神经系统检查有改善；6名儿童无变化，8名儿童的神经系统体征恶化。中位生存期为15.1周，1年总生存率为26.7%（标准误差11.4%）。
观察到的不良结果表明，鞘内注射噻替派对儿童LM的联合治疗作用不大。
