单中心儿童间变性大细胞淋巴瘤60例分析

Clinical analysis of 60 children with anaplastic large cell lymphoma in a single center

目的总结儿童间变性大细胞淋巴瘤(ALCL)的临床特征和治疗结果,并分析预后相关因素。方法收集2010年1月至2018年12月上海交通大学医学院附属上海儿童医学中心收治的病理诊断明确的初治ALCL患儿共60例(≤18岁),采用中国儿童肿瘤协作组-B细胞非霍奇金淋巴瘤-2010(CCCG-BNHL-2010)方案治疗。采用Kaplan-Meier方法计算总体生存率(OS)、无事件生存率(EFS)及无进展生存率(PFS);单因素行Log-Rank检验分析预后不良因素。结果纳入研究的60例ALCL患儿中男39例、女21例,发病年龄7.9(1.2~16.7)岁,有B症状[即发热和(或)夜间盗汗和(或)体重减轻]者43例(72%),乳酸脱氢酶(LDH)<2倍正常值上限者49例(82%)、2~<4倍正常值上限者11例(18%)。临床分期显示,Ⅰ期1例、Ⅱ期3例、Ⅲ期55例、Ⅳ期1例。间变性淋巴瘤激酶(ALK)免疫组织化学结果明确的患儿有58例,其中阳性53例(91%)。12例(20%)有实质脏器(心、肝、脾、肺、肾、胰)受累。本组患儿4年OS和EFS分别为(88±4)%和(76±6)%。将性别、B症状、LDH水平、ALK表达、临床分期、实质脏器是否受累分别进行预后单因素分析,仅LDH水平对患儿OS的影响有统计学意义(χ^(2)=6.571,P=0.010),但对EFS的影响差异均无统计学意义(均P>0.05)。截至末次随访,44例患儿处于持续缓解状态,随访时间50(13~119)个月。本组病例中13例出现疾病进展或复发(23%),其中3例进展或复发后直接放弃治疗,2例直接进展至死亡,8例接受二线和挽救治疗(6例末次随访仍存活)。进展或复发后病例的2年OS和PFS分别为(60±16)%和(16±14)%。本组治疗相关病死率5%(3/60),均为化疗后发生严重感染死亡。结论CCCG-BNHL-2010方案治疗儿童ALCL疗效良好,但治疗相关病死率偏高,方案安全性有待提高。ALCL进展或复发后经过有效二线治疗仍可获得较高生存率。LDH≥2倍正常值上限是预后不良因素。

Objective To summarize the clinical features,treatment outcome and prognostic factors of childhood anaplastic large cell lymphoma(ALCL).Methods Clinical data of 60 newly diagnosed and biopsy-proven ALCL pediatric patients(≤18 years of age)at Shanghai Children′s Medical Center,Shanghai Jiao Tong University School of Medicine from January 2010 to December 2018 were collected.All patients were treated with the Chinese Children Cancer Group-B cell-non-Hodgkin Lymphoma 2010(CCCG-BNHL-2010)regimen.Overall survival(OS),event free survival(EFS)and progression free survival(PFS)rates were calculated by the Kaplan-Meier method.Univariate analysis was performed with Log-Rank test to find factors of poor prognosis.Results Among 60 ALCL patients included in the current study,39 were males and 21 females,the age of onset was 7.9(1.2-16.7)years.Among all cases,43(72%)had B syndrome(any of the following:fever,drenching,weight loss).Forty-nine(82%)cases had lactate dehydrogenase(LDH)levels<2 times upper limit of normal(ULN)and 11(18%)cases had LDH levels 2-<4 times ULN.The distribution of stages was stageⅠ,Ⅱ,Ⅲ,andⅣin 2%(1/60),5%(3/60),92%(55/60),and 2%(1/60)of patients,respectively.Of 58 cases who had results of anaplastic lymphoma kinase(ALK)immunohistochemical staining,53(91%,53/58)cases were positive.Visceral involvement was observed in 12 patients(20%).The 4-year OS and EFS rates were(88±4)%and(76±6)%for the entire group,respectively.Univariate analysis for gender,B symptoms,LDH level,ALK expression,clinical stage and visceral involvement showed that only LDH level correlated with an inferior OS rate(χ^(2)=6.571,P=0.010)while not correlated with EFS rate.No independent risk factor for disease progression or recurrence was found by Logistic regression.Up to the last follow-up,44 cases were continuously at complete remission state,and their follow-up time was 50(13-119)months.Of 13(23%)cases experienced disease progression or relapse,3 cases abandoned treatment,2 cases progressed to death,8 cases received second line or salvage treatment(6 survived at last follow-up).For post progression or relapse cases,the 2-year OS and PFS rates were(60±16)%and(16±14)%,respectively.The treatment related death occurred in 3 cases(5%)and all of them were due to severe infection during the chemotherapy.Conclusions The efficacy of CCCG-BNHL-2010 regimen in the treatment of children with ALCL was good.However,the safety needs to be improved as the treatment-related mortality in the present study was slightly higher.Efficient second line or salvage treatment can achieve cure in pediatric patients post progression or recurrence.LDH≥2 times ULN was associated with worse prognosis.