伴第21号染色体内部扩增儿童急性B淋巴细胞白血病的临床特征及预后分析

Clinical features and prognosis of B⁃cell acute lymphoblastic leukemia children with intrachromosomal amplification of chromosome 21

目的探讨伴第21号染色体内部扩增(iAMP21)的儿童急性B淋巴细胞白血病(B-ALL)的临床特征及预后。方法回顾性分析2019年1月至2020年12月于福建医科大学附属协和医院确诊并按照中国儿童肿瘤协作组儿童急性淋巴细胞白血病2015(CCCG-ALL-2015)方案化疗的233例B-ALL患儿资料。采用ETV6-RUNX1探针荧光原位杂交法检测患儿化疗前骨髓液iAMP21是否阳性,并依此将患儿分为iAMP21组和非iAMP21组。iAMP21组患儿均接受CCCG-ALL-2015中危组方案诱导化疗,非iAMP21组患儿依据临床危险度接受不同强度化疗。比较两组患儿临床病理特征,分析伴iAMP21患儿疗效及预后。结果233例B-ALL患儿中检出伴iAMP21患儿5例(2.1%)。iAMP21组中位血红蛋白浓度高于非iAMP21组[99 g/L(71~148 g/L)比74 g/L(30~156 g/L);U=268.50,P=0.043];iAMP21组5例和非iAMP21组228例中分别有4例和53例表现为骨关节疼痛,两组骨关节疼痛发生率差异有统计学意义(χ^(2)=8.53,P=0.017);两组中不同性别、年龄、白细胞计数、血小板计数、肝脾大患儿比例差异均无统计学意义(均P>0.05)。伴iAMP21的5例患儿中,伴CRLF2高表达1例,伴IKZF1第1号至第8号外显子杂合缺失1例,此2例患儿巩固治疗后微小残留病(MRD)仍未转阴,遂接受嵌合抗原受体T细胞(CAR-T)及造血干细胞移植治疗;其余3例伴iAMP21患儿诱导缓解治疗后MRD均转阴。至2021年10月末次随访,5例伴iAMP21患儿均无病生存。结论伴iAMP21的儿童B-ALL发病率约2%,患儿易出现骨关节疼痛症状,贫血程度相对较轻,经积极治疗后部分患儿效果仍欠佳。

Objective To investigate the clinical features and prognosis of B⁃cell acute lymphoblastic leukemia(B⁃ALL)children with intrachromosomal amplification of chromosome 21(iAMP21).Methods The data of 233 children diagnosed with B⁃ALL who received chemotherapy according to Chinese Children Cancer Group(CCCG)⁃acute lymphoblastic leukemia⁃2015(CCCG⁃ALL⁃2015)protocol in the Affiliated Union Hospital of Fujian Medical University from January 2019 to December 2020 were retrospectively analyzed.These patients were divided into iAMP21 group and non⁃iAMP21 group according to whether iAMP21 was positive in the bone marrow fluid of children before chemotherapy based on ETV6⁃RUNX1 probe fluorescence in situ hybridization.Children in iAMP21 group received CCCG⁃ALL⁃2015 intermediate⁃risk group regimen induction chemotherapy,while children in non⁃iAMP21 group received different intensities of chemotherapy according to the clinical risk classification.The clinicopathological characteristics of patients were compared in both groups,the therapeutic efficacy and prognosis of B⁃ALL children with iAMP21 was analyzed.Results iAMP21 was found in 5(2.1%)of 233 B⁃ALL children.The median hemoglobin concentration in iAMP21 group was higher than that in non⁃iAMP21 group[99 g/L(71-148 g/L)vs.74 g/L(30-156 g/L);U=268.50,P=0.043];there were 4 cases(80%)with bone pain in iAMP21 group(5 cases)and 53 cases(23.2%)with bone pain in non⁃iAMP21 group(228 cases),and the difference in the osteoarticular pain incidence of both groups was statistically significant(χ^(2)=8.53,P=0.017).There were no significant differences in the proportion of patients with different gender,age,white blood cell counts,platelet counts,hepatosplenomegaly between the two groups(all P>0.05).Among 5 children with iAMP21,1 patient was detected with high CRLF2 expression and 1 patient with IKZF11-8 exon loss of heterozygosity.The above mentioned two children with iAMP21,whose minimal residual disease(MRD)were still positive after consolidation therapy,and then they received chimeric antigen receptor T⁃cell treatment and hematopoietic stem cell transplantation.MRD of the other 3 children with iAMP21 turned negative after induction therapy.Up to the last follow⁃up in October 2021,5 patients with iAMP21 had disease⁃free survival.Conclusions The incidence of B⁃ALL children with iAMP21 is about 2%.These patients are prone to osteoarticular pain and have relatively mild anemia.The curative effect of some children is still poor after active treatment,which needs to be further clarified with more samples.