Dupuis-Girod S, Hartmann O, Benhamou E, Doz F, Mechinaud F, Bouffet E, Coze C, Kalifa C
Service d'oncologie pédiatrique, Institut Gustave-Roussy, Villejuif, France.
Bull Cancer. 1997 Mar;84(3):264-72.
Craniospinal irradiation is the gold standard treatment used in non metastatic medulloblastoma as prophylaxis against central nervous system (CNS) metastases. However, given the severe late effects caused by this procedure in children under 3 years of age, most pediatric oncologists are currently treating these patients with conventional chemotherapy in order to postpone or even avoid irradiation. In the French Society of Pediatric Oncology (SFOP) this attitude has been adopted since 1990. Among the patients treated without radiotherapy, 20 relapsed while on conventional chemotherapy and were entered in a study of high-dose chemotherapy (HDC) followed by autologous bone marrow transplantation (ABMT). Their median age at diagnosis was 23 months (range: 5-71 months) and the relapse occurred at a median time of 6.3 months after the initiation of chemotherapy. Complete surgical removal of the local relapse was the first treatment in 4/20 patients who were not evaluable for response. Sixteen of the 20 patients had measurable disease at the primary site (9 patients), or at metastatic sites (3 patients) or both (4 patients). The conditioning regimen consisted of combination busulfan 600 mg/m2 over 4 days and thiotepa 900 mg/m2 over 3 days. After recovery from aplasia, patients with a local relapse received local radiotherapy limited to posterior fossa. Among the 16 patients with measurable disease, 6 complete responses, 6 partial responses, 3 non response, were observed following HDC (response rate 75%). One patient was not evaluable. For the 20 patients, the event free survival (EFS) is 50%. Among the surviving patients, the median follow-up is 39.5 months post BMT (range: 21-92 months). Ten patients who developed a local relapse or local progression are alive with non evidence of disease (NED) without craniospinal irradiation. Among the 7 patients who developed a metastases or progression of metastases, only 1 is alive. Toxicity was high but manageable. One complication-related death occurred 1 month post BMT. With a 75% response rate, this HDC proved to be very efficient in relapsed medulloblastoma. A longer follow-up is necessary to demonstrate whether, after a local relapse, HDC could replace craniospinal irradiation as prophylaxis against CNS metastases.
颅脊髓照射是用于非转移性髓母细胞瘤预防中枢神经系统（CNS）转移的金标准治疗方法。然而，鉴于该治疗方法对3岁以下儿童会造成严重的晚期影响，目前大多数儿科肿瘤学家采用传统化疗来治疗这些患者，以推迟甚至避免照射。自1990年以来，法国儿科肿瘤学会（SFOP）一直采取这种态度。在未接受放疗的患者中，20例在接受传统化疗时复发，并进入了一项高剂量化疗（HDC）联合自体骨髓移植（ABMT）的研究。他们诊断时的中位年龄为23个月（范围：5 - 71个月），复发发生在化疗开始后的中位时间6.3个月。4/20例对反应不可评估的患者中，首次治疗是对局部复发进行完整手术切除。20例患者中有16例在原发部位（9例）、转移部位（3例）或两者（4例）有可测量的疾病。预处理方案包括4天内给予白消安600 mg/m²和3天内给予噻替派900 mg/m²。再生障碍恢复后，局部复发的患者接受限于后颅窝的局部放疗。在16例有可测量疾病的患者中，HDC后观察到6例完全缓解、6例部分缓解、3例无反应（反应率75%）。1例患者不可评估。对于这20例患者，无事件生存期（EFS）为50%。在存活患者中，BMT后的中位随访时间为39.5个月（范围：21 - 92个月）。10例发生局部复发或局部进展的患者在未进行颅脊髓照射的情况下无疾病证据（NED）存活。在7例发生转移或转移进展的患者中，仅1例存活。毒性很高但可控。1例与并发症相关的死亡发生在BMT后1个月。HDC的反应率为75%，在复发性髓母细胞瘤中被证明非常有效。需要更长时间的随访来证明在局部复发后，HDC是否可以替代颅脊髓照射来预防CNS转移。
