Busca A, Miniero R, Besenzon L, Cordero di Montezemolo L, Cenni M, Fagioli F, Sandri A, Vassallo E, Ricardi U, Madon E
Department of Pediatrics, University of Turin, Italy.
Childs Nerv Syst. 1997 Nov-Dec;13(11-12):572-7. doi: 10.1007/s003810050142.
Despite improvements in neurosurgical and neuroradiotherapeutic techniques, children with malignant brain tumors have a dismal prognosis. In an attempt to improve the efficacy of cytotoxic therapy, dose intensification of effective chemotherapeutic agents followed by autologous bone marrow transplantation (BMT) has been tried. Between May 1991 and August 1996, high-dose chemotherapy and autologous BMT were administered to 11 children with malignant brain tumors: 10 had recurrent (n = 8) or progressive (n = 2) disease, and 1 was treated before progression. The histological diagnoses were medulloblastoma (3), glioblastoma multiforme (2), supratentorial PNET (2), ependymoma (2), anaplastic astrocytoma (1), and anaplastic oligodendroglioma (1). In 6 of the 11 patients measurable disease was present at the time of BMT. The preparative regimen included BCNU 600 mg/m2 and VP16 1500 mg/m2 in 5 cases, and thiotepa 900 mg/m2 and VP16 1500 mg/m2 in 6 cases. The median times to achieve a neutrophil count over 0.5 x 10(9)/l and a platelet count over 50 x 10(9)/l were 14 and 28 days, respectively. The overall incidence of severe toxicity (grade III-IV) was 18% and consisted of oropharyngeal mucositis and diarrhea. Among the 6 patients with measurable disease at the time of BMT there were 2 with stable disease, whereas 4 patients had tumor progression: all these patients died of tumor recurrence 2-10 months after BMT. Five patients in whom there was no evidence of disease at the time of BMT are alive and free of progression with a median follow-up of 20 months (range 3-67). These preliminary results show that high-dose chemotherapy and BMT may be effective in children with malignant brain tumors. Etoposide-containing regimens seem to have significant activity in this setting, and the toxicity was manageable. The most important variable prognostic for progression-free survival is the disease status at the time of transplantation.
尽管神经外科手术和神经放射治疗技术有所改进，但恶性脑肿瘤患儿的预后仍然很差。为了提高细胞毒性疗法的疗效，人们尝试了增加有效化疗药物的剂量强度，随后进行自体骨髓移植（BMT）。1991年5月至1996年8月期间，对11例恶性脑肿瘤患儿进行了高剂量化疗和自体BMT：10例为复发（n = 8）或进展性（n = 2）疾病，1例在疾病进展前接受治疗。组织学诊断为髓母细胞瘤（3例）、多形性胶质母细胞瘤（2例）、幕上原始神经外胚层肿瘤（2例）、室管膜瘤（2例）、间变性星形细胞瘤（1例）和间变性少突胶质细胞瘤（1例）。11例患者中有6例在进行BMT时存在可测量的疾病。预处理方案包括5例使用卡莫司汀600 mg/m²和依托泊苷1500 mg/m²，6例使用塞替派900 mg/m²和依托泊苷1500 mg/m²。中性粒细胞计数超过0.5×10⁹/L和血小板计数超过50×10⁹/L的中位时间分别为14天和28天。严重毒性（III-IV级）的总体发生率为18%，包括口腔黏膜炎和腹泻。在进行BMT时存在可测量疾病的6例患者中，2例病情稳定，而4例患者肿瘤进展：所有这些患者均在BMT后2 - 10个月死于肿瘤复发。5例在进行BMT时无疾病证据的患者存活且无疾病进展，中位随访时间为20个月（范围3 - 67个月）。这些初步结果表明，高剂量化疗和BMT可能对恶性脑肿瘤患儿有效。含依托泊苷的方案在这种情况下似乎具有显著活性，且毒性可控。无进展生存期最重要的预后变量是移植时的疾病状态。
