儿童B细胞性非霍奇金淋巴瘤2001方案临床报告

Clinical report on protocol B-NHL 2001 for childhood B-non Hodgkin's lymphoma

目的分析2001方案短程化疗对儿童B细胞性非霍奇金淋巴瘤(B-NHL)及间变大细胞型淋巴瘤(ALCL)的疗效。方法根据国外发达国家报道及本研究组前期CCCG-97方案结果,对CCCG-97方案的适应证、分组标准、治疗强度及治疗时间进行修正,制定B-NHL2001方案。根据分期和血清乳酸脱氢酶(LDH)水平将患儿分为低危组(R1组)、中危组(R2组)和高危组(R3组),分别接受3、5和6个疗程的短程化疗。对2001年1月至2007年6月上海交通大学医学院附属上海儿童医学中心血液/肿瘤科明确诊断为B-NHL(伯基特型、弥漫大B细胞性和未能进一步行病理形态分型)和ALCL的连续首诊病例进行分析。随访至2007年12月,采用Kaplan-Meier法计算生存率。结果研究期间纳入48例患儿,有3例(Ⅰ期1例,Ⅲ期2例)在1个疗程化疗好转后家长决定终止治疗未进入统计。有效数据45例,男35例,女10例。年龄10个月至15.5岁,平均7.1岁,中位年龄6.3岁;Ⅰ期2例,Ⅱ期17例,Ⅲ期18例,Ⅳ期8例;R1组2例,R2组14例,R3组29例。原发部位:腹腔23例,鼻咽部7例,外周淋巴结7例,皮下组织1例,纵隔1例,腮腺2例,股骨、髋骨各1例,右胸壁1例,广泛胸腹腔病变难以确定原发病灶1例。病理分型:伯基特型14例,弥漫大B细胞性13例,ALCL3例,B细胞性(非淋巴母细胞性,未能进一步行病理形态分型)15例。2个疗程化疗后获得完全缓解(CR)41例;因有残留病灶而在3个疗程化疗后行2次手术,病理活检证实无肿瘤细胞确定为CR2例。CR率为95.6%(43/45例)。2例(Ⅲ、Ⅳ期各1例)未获CR,其中1例3个疗程化疗后仍有残留病灶行2次手术,病理活检证实仍为肿瘤组织。随访至2007年12月,40/43例(88.9%)持续CR中,均已完成治疗。随访6～77个月,平均26.9个月,中位随访时间为19个月。复发3例(Ⅲ期2例,Ⅳ期1例),其中1例为盆腔原发部位复发、1例骨髓复发、1例转移性脑膜复发,复发时间分别为诊断后5、6和8个月。估计5年无病生存率(EFS)为88.3%。结论B-NHL2001方案估计5年EFS为88.3%,提示该方案有合理性,值得进一步扩大病例验证。

Objective To analyze the efficacy of protocol B-NHL2001 for B cell non-Hodgkin＇s lymphoma （B-NHL） and anaplastic large cell lymphoma（ALCL）. Methods Depending on the reports from developed country and the results of our former protocol NHL-CCCG-97, the protocol B-NHL 2001 revised the eligibility, grouping criteria, intensity of chemotherapy and time of treatment. Patients were divided into low, middle and high risk groups （R1 ,R2, R3） based on staging and the level of lactate dehydrogenase （LDH） , and given 3, 5, and 6 courses of chemotherapy respectively. All the patients from 2001 to June 2007 were enrolled. The software of SPSS 11.0 was used and the event free survival was generated by Kaplan-Meier. Results There were 45 patients in total, 35 males and 10 females. The average age was 7.1 years （ranged from 10 months to 15.5 years） , medium age was 6.3 years. Two patients were in stage Ⅰ , 17 in stage Ⅱ, 18 in stageⅢ and 8 in stageⅣ. The original tumor was found in abdomen for 23 patients, nose-pharynges for 7, periephel lymph-nodes for 7, cutaneous for 1, mediastinum for 1, bone for 2, mumps for 2 , chest wall for 1 and extensive infiltration in chest and abdomen for 1. They were pathologically sub-classified as Burkitt＇s for 14 cases,large B cell for 13 ,anaplastie large cell for 3 and B-NHL（ non-lymphoblastic, no further sub-classification） for 15. Two patients were allocated into low risk group （R1）, 14 into middle risk group（ R2 ） and 29 into high risk group （R3）. Three were ruled off the analysis because of abandoning treatment by parents after 1 course therapy without progressive disease （ 1 of stage Ⅰ , 2 of stage Ⅲ ） Forty-one of 45 patients reached complete response （CR） after 2 courses of chemotherapy. Another 3 received second look surgery because of residual disease after 3 courses therapy, 2 of them were proved CR （ no tumor cells in residual mass） by pathology, 1 with alive tumor cells. In total, 43 of 45 reached CR （95.5%） , one of stage Ⅲ and one of stage Ⅳ never reached CR. To Dec 2007, 40 of them kept in CR（88.9% ） with 6 to 77 months follow-up, average 26.9 months, medium 19 months. Three cases relapsed at original place, bone marrow and in cranial （2 of stage Ⅲ and 1 of stage Ⅳ ） which occurred in 5,6 and 8 months. The estimated 5-year event free survival （EFS） was 88.3%. Conclusions The estimated 5-year event free survival indicated that B-NHL 2001 was reasonable for both B-NHL and ALCL and worth to enroll more patients.