复发儿童B细胞淋巴瘤19例临床病理特征及治疗预后分析

Clinical pathologic characteristics and treatment outcomes of 19 relapsed pediatric B-cell lymphoma

目的总结复发的儿童成熟B细胞淋巴瘤的资料，探讨复发的危险因素和复发后可行的治疗方案。方法收集2006年1月至2015年6月北京儿童医院收治的212例B细胞淋巴瘤患儿资料，全部患儿按照北京儿童医院-B细胞淋巴瘤方案进行治疗。其中19例患儿复发，回顾性分析其治疗前及复发后的临床、病理特征，总结复发后的治疗结果并追踪其预后。结果212例患儿中19例复发：初诊时的中位年龄5岁5月龄。治疗前尿酸384（121～713）μmol/L，乳酸脱氢酶（LDH）1 323（146～6 370）U/L；单部位复发10例，多部位复发9例；17例伯基特淋巴瘤，2例弥漫性大B细胞淋巴瘤，Ⅱ期2例，Ⅲ期3例，Ⅳ期14例；B组6例，C组13例；骨髓侵犯者9例、中枢侵犯者10例；早期合并肿瘤溶解综合征者6例，存在化疗延迟者13例。复发后治疗：10例患儿接受挽救性治疗，分别接受利妥昔单抗1～4个疗程不等的高强度二线化疗。3例患儿接受自体干细胞移植术。无化疗或感染相关并发症所致死亡，达完全缓解（CR）者3例。212例患儿中位随访时间47（1～131）个月，5年无事件生存率（EFS）为（89.4±0.2）%，19例复发患儿5年总生存率（OS）为（21.1±0.1）%，复发后CR率为30%，复发患儿死因均为原发病进展所致。单因素分析显示复发相关的危险因素分别为病初存在巨大瘤灶、Ⅳ期、颌面部及中枢神经系统侵犯、病初LDH〉1 000 U/L、存在延迟化疗、第7天评估肿瘤缩小〈25%，中期评估有残留病灶（P均〈0.01）。结论治疗中及停药早期复发者预后差，目前尚无有效及可行的治疗方案，远期复发患儿若对挽救性化疗敏感有再治愈的可能，因此减少复发是提高患儿预后的关键。

ObjectiveTo review the clinical-pathology characteristics of 19 relapsed pediatric mature B cell lymphoma and to find the risk factors for recurrence and the feasible treatment after relapse.MethodData of 212 pediatric B cell lymphomas cases in Beijing Children′s Hospital from January 2006 to June 2015 were collected retrospectively. All the patients were treated according to the B cell lymphoma regimen of Beijing Children′s Hospital. During the study period, 19 of 212 cases were relapsed; the clinio-pathological characteristics of relapsed patients before treatment and after relapse were analyzed retrospectively, the treatment outcomes after relapse were summarized and the patients were followed-up.ResultNineteen of 212 cases had relapsed disease, for these relapsed patients： the median age at initial diagnosis was 5.5 years old, the median level of uric acid was 384（range, 121-713）μmol/L, the median level of lactate dehydrogenase（LDH） was 1 323（range, 146-6 370）U/L. Among 19 relapsed patients, 10 had local relapse and 9 had multiple relapses; 17 were Burkitt′s lymphoma and 2 were diffuse large B cell lymphoma. Staging： 2 cases were stageⅡ, 3 cases were stage Ⅲ and 14 cases were stage Ⅳ. Risk group： 6 cases were group B and 13 cases were group C. Nine cases had bone marrow involvement and 10 cases had central nervous system（CNS） involvement. Acute tumor lysis syndrome was seen in 6 cases during the early treatment and 13 cases had delayed treatment. Treatment after relapse： 10 cases received further treatment after relapse （rituximab ＋ 1-4 courses high intensity second-line chemotherapy）, 3 cases received autologous stem cell transplantation. There was no chemotherapy or infection related death, 3 cases achieved complete remission （CR）. For all the 212 patients, the median follow-up time was 47 （range, 1-131）months and the 5-year event free survival（EFS）rate was （89.4±0.2）%. For the 19 relapse cases, the 5-year overall survival （OS） rate was （21.1±0.1）%, CR rate after relapse was 30%, patients died of the progression of the primary disease, no treatment related death occurred. Univariate analyses showed that bulky disease, stage Ⅳ, maxillofacial and CNS involvement, LDH〉1 000 U/L, delay treatment, day 7 evaluation shrink 〈25%, residual diseases after 3 months treatment are relapse risk factors （all P〈0.01）.ConclusionPatients relapse during the treatment or at the early stage after the end of all chemotherapy have poor prognosis. So far there is no effective method for early relapse patients; the late relapse patients had the possibility of CR if they are sensitive to salvage treatment. In conclusion, to improve the outcome, the key point is to reduce the relapse.