儿童复发急性淋巴细胞白血病52例临床分析

Clinical analysis of 52 children with relapsed acute lymphoblastic leukemia

目的探讨儿童复发急性淋巴细胞白血病(ALL)的临床特征及预后相关因素。方法回顾性分析2010年1月至2019年4月山西省儿童医院诊治的52例复发ALL患儿临床资料。分析患儿临床特征及复发后预后相关因素。结果截至2019年5月1日,52例患儿中5例因诊断后放弃治疗而失访。47例随访成功患儿中位初诊年龄60个月(11~168个月),中位复发时间21个月(2~112个月),复发后中位随访时间5.5个月(1.0~69.0个月),复发后2年总生存(OS)率31%。9例患儿获得第2次完全缓解后行异基因造血干细胞移植,中位移植时间为4.5个月(3.0~7.0个月),中位随访时间为22个月(4~69个月)。初诊白细胞计数<50×10^9/L与≥50×109/L复发患儿2年OS率分别为39%和13%(χ^2=5.623,P=0.018)。初诊标危、中危、高危患儿复发后2年OS率分别为72%、31%和8%(χ^2=10.068,P=0.007)。超早期复发、早期复发、晚期复发患儿复发后2年OS率分别为0、33%和79%(χ^2=30.066,P<0.01)。复发后化疗联合或不联合放疗、移植及未规律治疗患儿复发后2年OS率分别为57%、89%和0(χ^2=26.885,P<0.01)。Cox多因素分析结果显示,复发时间(HR=0.340,95%CI 0.146~0.789,P=0.012)为复发ALL患儿预后独立影响因素。相对于移植组,化疗联合或不联合放疗组及未规律治疗组死亡风险增高(HR=12.313,95%CI 1.266~119.758,P=0.031;HR=20.699,95%CI 2.230~192.129,P=0.008),提示造血干细胞移植为复发ALL患儿预后的保护因素。结论儿童ALL复发以超早期及早期复发为主,复发部位以骨髓复发常见,初诊中高危患者较多。初诊时危险度、初诊白细胞计数、复发时间、复发后治疗是影响预后的因素,其中复发时间及造血干细胞移植是影响预后的独立因素。

Objective To explore the clinical characteristics and prognostic factors of children with relapsed acute lymphoblastic leukemia(ALL).Methods The clinical data of 52 children with relapsed ALL in Children's Hospital of Shanxi Province from January 2010 to April 2019 were retrospectively analyzed.The clinical characteristics of the children were summarized and the prognostic factors after recurrence were analyzed.Results Till May 1,2019,5 out of 52 children gave up treatment after diagnosis and were lost to follow-up.For the remaining 47 children with successful follow-up,the median age at initial diagnosis was 60 months(11-168 months),the median time from initial diagnosis to relapse was 21 months(2-112 months),the median follow-up time was 5.5 months(1.0-69.0 months),and the 2-year overall survival(OS)rate after relapse was 31%.Nine patients accepted allogeneic hematopoietic stem cell transplantation after the second time complete remission,the median time from diagnosis to transplantation was 4.5 months(3.0-7.0 months),and the median follow-up time was 22 months(4-69 months).The 2-year OS rates in relapsed children with white blood cell count<50×10^9/L and≥50×10^9/L at initial diagnosis were 39%and 13%,respectively(χ^2=5.623,P=0.018).The 2-year OS rate after relapse in standard-risk,intermediate-risk and high-risk groups were 72%,31%and 8%,respectively(χ^2=10.068,P=0.007).The 2-year OS rate after relapse in very early relapse,early relapse and late relapse groups were 0,33%and 79%,respectively(χ^2=30.066,P<0.01).The 2-year OS rate after relapse in chemotherapy with or without radiotherapy group,transplantation group and irregular treatment group were 57%,89%and 0,respectively(χ^2=26.885,P<0.01).Cox multivariate analysis showed that relapse time was the independent risk factor affecting the prognosis of children with relapsed ALL(HR=0.340,95%CI 0.146-0.789,P=0.012).Compared with the transplantation group,the risk of death in the chemotherapy with or without radiotherapy group and the irregular treatment group was significantly higher(HR=12.313,95%CI 1.266-119.758,P=0.031;HR=20.699,95%CI 2.230-192.129,P=0.008),suggesting that hematopoietic stem cell transplantation is a protective factor for the prognosis of children with relapsed ALL.Conclusions The relapse of ALL in children mainly happens in very early and early time.The main part of relapse is bone marrow,and there are many high-risk patients at initial diagnosis.The risk group at initial diagnosis,white blood cell count at initial diagnosis,relapse time,and treatment after relapse are the risk factors affecting the prognosis,and the relapse time and hematopoietic stem cell transplantation are the independent prognostic factors.