CCCG-97和BFM-90方案治疗45例儿童成熟B细胞非霍奇金淋巴瘤的疗效

Comparison of the efficacy of CCCG-97 and BFM-90 protocols in the treatment for children with mature B-cell non-Hodgkin＇s lymphoma

目的探讨采用CCCG07方案和BFMOO方案治疗儿童成熟B细胞非霍奇金淋巴瘤（B—NHL）患者的疗效和不良反应。方法45例初治儿童成熟B—NHL患者中，Ⅱ期4例，Ⅲ期32例，Ⅳ期9例；Burkitt淋巴瘤（BL）21例，弥漫性大B细胞淋巴瘤（DLBCL）24例。45例患者分别接受CCCG-97方案（1999年6月至2004年12月收治的21例患者，中位年龄8．2岁）和BFM00方案（2005年1月至2008年12月收治的24例患者，中位年龄7．9岁）治疗，其中5例接受BFM00方案治疗的CD20阳性患者还采用利妥昔单抗治疗。接受CCCG07方案治疗的患者中，低危组1例，高危组20例；接受BFM00方案治疗的患者中，R1组2例，R2组7例，R3组15例。比较两种治疗方案的疗效和不良反应。结果全组45例患者的治疗有效率为88．9％，其中接受CCCG07方案治疗患者为95．2％，接受BFM00方案治疗患者为83．3％，差异无统计学意义（P=0．205）。全组患者的中位随访时间为62个月，5年无事件生存率为71．8％，其中Ⅲ＋Ⅳ期患者为69．1％。接受CCCG07方案和BFM-90方案治疗患者的3年无事件生存率分别为76．2％和75．0％，差异无统计学意义（P=0．975）。全组早期死亡4例，复发6例。接受CCCG07方案和BFM00方案治疗患者的复发率分别为19．0％和8．3％，差异无统计学意义（P=0．292）。接受CCCG-97方案治疗患者血液学毒性的发生率明显高于BFM00方案（P〈0．001），但严重的Ⅲ、Ⅳ级血液学毒性的发生率差异并无统计学意义（P=0．643）。接受CCCG07方案治疗患者黏膜炎的发生率明显低于BFM00方案（P〈0．001），而胃肠道反应的发生率明显高于BFM00方案（P=0．005）。接受利妥昔单抗治疗的5例患者中，2例Ⅲ期患者持续完全缓解，3例Ⅳ期患者死亡。结论采用正确的治疗策略和方案可明显提高儿童成熟B-NHL患者的生存率，CCCG07方案和BFM00方案的近、远期疗效相仿，不良反应患者均可耐受。

Objective The aim of this study was to evaluate the efficacy and toxicity of the CCCG- 97 and BFM-90 protocols in the treatment of pediatric patients with B-cell non-Hodgkin＇ s lymphoma （ B- NHL） retrospectively, and to explore the optimal therapeutic strategy. Methods Forty-five consecutive untreated patients （age of 18 years or less） with newly diagnosed B-NHL （including Burkitt Lymphoma and diffuse large B-cell lymphoma）, treated in our hospital between July 1999 and December 2008 were enrolled in this study. The patients were classified into 2 groups by different protocols. From July 1999 to December 2004, twenty-one 3- to 13.8-year-old children were enrolled in the CCCG-97 group, with 1 in stage I / Ⅱ, and 20 in stage m/IV （ st Jude staging）. From January 2005 to December 2008, twenty-four 2.8- to 14.1- year-old cases were enrolled in the BFM-90 group, with 3 in stage I/II, and 21 in stage Ⅲ/IV （St Jude staging）. The survival rates were evaluated by Kaplan-Meier analysis. Results Forty of the 45 patients （88.9%） reached complete response （CR） after 2 courses of chemotherapy. In the CCCG-97 group, the CR rate was 95.2% （20/21 pts）, while that in the BFM-90 group was 83.3% （20/24 pts）. At a median follow-up time of 62 （17 to 131 ） months, the 5-year event-free survival （EFS） was 71.8% for all patients,and 69.1% for Stage Ill^IV, respectively. In the CCCG-97 group, the 3-year EFS was 76.2%. In the BFM-90 group, it was 75.0%. There was no significant difference in survival rates between the CCCG-97 and BFM-90 groups （ P = 0.975 ）. Unfavorable events recorded were as follows ： Death of progression before achieving CR during induction therapy in 4 cases, and relapse after achieving CR in 6 cases. The relapse rates were 19.0% （4/21 pts） in the CCCG-97 group and 8.3% （2/24 pts） in the BFM-90 group, with a non-significant statistical difference （ P = 0. 292 ）. Major toxicities were myelosuppression and mucositis, especially in the BFM-90 group, but were tolerable and manageable, five patients in the BFM-90 group received rituximab, 2 patients （Stage III ） achieved CR, while the other 3 patients （Stage IV ） had progressive disease or relapse. Conclusions Short-pulse and intensive chemotherapy, stratified according to stage of disease, can improve the survival rate of pediatric mature B-NHL. The efficacy of the CCCG-97 protocol and BFM-90 protocol is comparable and the toxicity is tolerable.