ALL-XH-99方案治疗儿童急性淋巴细胞性白血病疗效分析

目的：由上海新华医院／上海儿童医学中心制定的治疗儿童急性淋巴细胞性白血病（ALL）的ALL-XH-99方案已在该院实施10年了。该文旨在评估应用此方案治疗儿童急性淋巴细胞性白血病（ALL）的疗效，并探讨儿童ALL的预后因素。方法：回顾分析1998年1月～2007年4月在该院采用ALL-XH-99方案治疗的儿童ALL的临床资料。该研究在ALL-XH-99方案的基础上作了一些小的修订，即对高危患儿也未给予颅脑放射治疗。采用Kaplan-Meier方法评估患儿的无事生存率（EFS），组间患儿EFS差异用log-rank检验。采用逐步Cox比例风险模型分析ALL的预后因素。结果：115 例患儿得到了全程的ALL-XH-99方案治疗，其中低、中、高危患儿分别为62、12、41人。这115例患儿总的5年EFS率为（69.0±5.0）%，其中低危、中危、高危组5年的EFS率分别为(82.0±6.0)%、(77.0±15.0)% 和 (43.0±11.0)% （P< 0.01）。16例(13.9%)复发，复发的中位时间为17个月。所有病例均未采取颅脑放疗，中枢神经系统白血病复发率（2/115，1.7%）并未高于既往报道。多因素分析显示白血病危险分度、t(9;22)/bcr/abl融合基因和白细胞计数是儿童ALL独立的不利预后因素，其风险比例分别为1.867、3.397和2.236。结论：采用ALL-XH-99方案治疗儿童ALL疗效满意，取得了与发达国家类似的EFS率。t(9；22)/bcr/abl融合基因为儿童ALL最重要的不利预后因素。在强有力的系统化疗和鞘内注射条件下，对所有患儿可取消颅脑放疗以减少副作用。

Therapeutic effectiveness of the ALL-XH-99 protocol for childhood acute lymphoblastic leukemia

OBJECTIVE: The ALL-XH-99 protocol for the treatment of childhood acute lymphoblastic leukemia (ALL) has been performed in the Union Hospital for 10 years. This study aimed to evaluate the therapeutic effectiveness of the protocol for childhood ALL and to investigate the prognostic factors for childhood ALL. METHODS: This is a retrospective study. The eligible patients were treated with the ALL-XH-99 protocol. However a minor modification based on the ALL-XH-99 protocol was performed in this study, i.e., the high-risk patients as the low- and moderate-risk patients were not administered with cranial irradiation. Event-free survival (EFS) was evaluated using the Kaplan-Meier method and the differences of the EFS among groups were compared with the log-rank test. Prognostic factors for childhood ALL were investigated by the stepwise Cox proportional hazard model. RESULTS: One hundred fifteen patients were eligible for the ALL-XH-99 protocol clinical study. The 115 patients consisted of 62 low-risk, 12 moderate-risk and 41 high-risk patients. The overall EFS at 5 years in the 115 patients was 69.0 +/- 5.0%. The 5-year-EFS in the low-risk, moderate-risk and high-risk patients was 82.0 +/- 6.0%, 77.0 +/- 15.0% and 43.0 +/- 11.0%, respectively (P <0.01). Relapse occurred in 16 patients (13.9%) in a median time of 17 months. Without administering cranial irradiation to all of the patients, the incidence of CNS leukemia relapse (2/115, 1.7%) was not higher than that previously reported. Multivariate analysis showed that the risk degree of leukemia, the presence of t (9; 22)/bcr/abl fusion gene and leukocyte count were independent adverse prognostic factors for ALL and their hazard ratio was 1.867, 3.397 and 2.236 respectively. CONCLUSIONS: The therapeutic effectiveness of the ALL-XH-99 protocol for childhood ALL is satisfactory, with an EFS rate comparable to that of the developed countries. t (9; 22)/bcr/abl is the most important adverse independent prognostic factor for childhood ALL. Cranial irradiation may be eliminated to reduce late adverse effects in all of ALL patients.