Johnson D B, Thompson J M, Corwin J A, Mosley K R, Smith M T, de los Reyes R A, Daly M B, Petty A M, Lamaster D, Pierson W P
J Clin Oncol. 1987 May;5(5):783-9. doi: 10.1200/JCO.1987.5.5.783.
Employment of postoperative brain irradiation in the initial management of high-grade malignant glial tumors has now become standard. The addition of conventional chemotherapy to irradiation has not significantly improved median survival beyond 1 year. We treated 25 consecutive patients (13 pilot patients and 12 protocol patients) with histologically confirmed unresectable grade 3 or 4 malignant gliomas with high-dose BCNU (carmustine) followed by autologous bone marrow transplantation and whole brain irradiation. Within 3 weeks of initial surgery, each patient had autologous bone marrow stored (median 2 X 10(8) nucleated cells/kg), and then received BCNU 1,050 mg/m2 intravenously (IV). Peripheral granulocytes recovered (greater than 500/microL) at a median of 19 days (range, 10 to 37 days), and platelets recovered (greater than 20,000/microL) at a median of 18 days (range, 13 to 40 days), following bone marrow infusion. Patients received 60 Gy whole brain irradiation when granulocytes were greater than 1,500/microL. Toxicity was well tolerated. Nausea occurred in 19 patients (76%); however, only eight patients (32%) experienced vomiting (mild in three, moderate in five). Eleven patients (44%) did not require empiric antibiotics, six of whom never developed an absolute granulocyte count less than 500/microL. Three patients with a poor performance status died early (one seizure with vomiting and asphyxiation; one, klebsiella urinary tract infection (UTI) with bacteremia; one, candidal pneumonia), and one additional patient who was performing well died of pulmonary hemorrhage. The 13 pilot patients have now been followed for a median of 23 months, with a significant survival advantage compared with the 52 consecutive historical control patients who received similar surgery and radiotherapy without high-dose BCNU (P = .037). The overall study group of 25 patients also has a significant survival advantage when compared with the same historical control group, with a projected median survival of 26 months (P = .007). This new approach using early postoperative intensive therapy consisting of high-dose BCNU, autologous bone marrow transplantation, and whole brain irradiation appears to significantly improve survival.
术后脑部放疗用于高级别恶性胶质瘤的初始治疗现已成为标准治疗方法。在放疗基础上加用传统化疗，并未使中位生存期显著延长超过1年。我们连续治疗了25例经组织学确诊为不可切除的3级或4级恶性胶质瘤患者（13例试点患者和12例方案患者），给予大剂量卡莫司汀（BCNU）治疗，随后进行自体骨髓移植和全脑放疗。在初次手术后3周内，为每位患者储存自体骨髓（中位值为2×10⁸有核细胞/kg），然后静脉注射1050mg/m²的BCNU。骨髓输注后，外周血粒细胞中位19天恢复（范围为10至37天），血小板中位18天恢复（范围为13至40天）。当粒细胞大于1500/μL时，患者接受60Gy全脑放疗。毒性反应耐受性良好。19例患者（76%）出现恶心；然而，只有8例患者（32%）发生呕吐（3例轻度，5例中度）。11例患者（44%）无需经验性使用抗生素，其中6例患者绝对粒细胞计数从未低于500/μL。3例身体状况较差的患者早期死亡（1例因癫痫伴呕吐和窒息；1例因克雷伯菌尿路感染伴菌血症；1例因念珠菌肺炎），另外1例身体状况良好的患者死于肺出血。13例试点患者目前中位随访23个月，与52例接受类似手术和放疗但未使用大剂量BCNU的连续历史对照患者相比，具有显著的生存优势（P = 0.037）。与同一历史对照组相比，25例患者的总体研究组也具有显著的生存优势，预计中位生存期为26个月（P = 0.007）。这种采用术后早期强化治疗，包括大剂量BCNU、自体骨髓移植和全脑放疗的新方法似乎能显著提高生存率。
