儿童急性淋巴细胞白血病治疗失败的相关因素分析

The Factors Related to Treatment Failure in Children with Acute Lymphoblastic Leukemia

目的:分析儿童急性淋巴细胞白血病(ALL)接受CCLG-ALL-2008方案治疗的临床疗效和治疗失败的相关因素。方法:回顾性分析2008年3月1日至2012年12月31日在苏州大学附属儿童医院新诊断为ALL并接受CCLG-ALL-2008方案治疗的400例患儿的临床资料,并随访到2019年10月,记录患儿复发和死亡时间及死亡原因。治疗失败定义为复发、非复发性死亡和二次肿瘤。结果:随访10年,共有152例患儿出现复发或者非复发性死亡,治疗失败率为38%,其中复发122例(80.3%),非复发性死亡30例(19.7%)。非复发性死亡包括治疗相关性死亡7例(占23.3%,感染死亡4例,出血死亡3例),骨髓微小残留病灶(MRD)持续阳性8例(占26.7%),经济原因放弃治疗15例(占50%)。按照时间构成,极早期复发37例(30%),早期复发38例(31%),晚期复发47例(39%)。按照复发部位构成,单纯骨髓复发107例,单纯睾丸复发3例,单纯中枢神经系统复发3例,骨髓+睾丸复发5例,骨髓+中枢神经系统复发4例。死亡的89例患儿以骨髓复发为主,其次是神经系统。初诊白细胞数≥50×109/L、免疫表型为T细胞和第12周MRD+为影响患儿复发的独立预后因素。年龄≥10岁、初诊白细胞数≥50×109/L、化疗d 15骨髓状态为M3和第12周骨髓MRD+为治疗失败的独立危险因素。随访10年无一例发生二次肿瘤。结论:复发是治疗失败的最主要原因,初诊白细胞数、免疫表型和第12周骨髓MRD是复发的独立预后因素。因经济因素导致治疗失败是无复发治疗失败的主要原因。

Objective:To analyze the efficacy of CCLG-ALL-2008 protocol and the related factors of treatment failure in children with acute lymphoblastic leukemia(ALL).Methods:The clinical data of 400 children newly-diagnosed ALL in Children’s Hospital of Soochow University from March 1,2008 to December 31,2012 was retrospectively analyzed.All the children accepted CCLG-ALL-2008 protocol,and were followed-up until October 2019.The dates of relapse,death and causes of death were recorded.Treatment failure was defined as relapse,non-relapse death,and secondary tumor.Results:Following-up for 10 years,there were 152 cases relapse or non-relapse death,the treatment failure rate was 38%,including 122 relapse(80.3%),30 non-relapse deaths(19.7%) which included 7 cases(4 cases died of infection and 3 cases died of bleeding) died of treatment(23.3% of non-relapse deaths),8 cases died of minimal residual disease(MRD) continuous positive(26.7% of non-relapse deaths) and 15 cases died of financial burden(50% of non-relapse deaths).According to the relapse stage,37 cases(30%) in very early stage,38 cases(31%) in early stage,and 47 cases(39%) in late stage,while according to the relapse site,107 cases relapsed in bone marrow,3 cases in testis,3 cases in central nervous system(CNS),5 cases in bone marrow plus testis and 4 cases in bone marrow plus CNS.Bone marrow relapse was the main cause of death in 89 cases,followed by nervous system.Initially diagnosed WBC count(≥50×109/L),T-cell immunophenotype,and MRD-positive at week 12 were the independent risk prognostic factors for relapse in children with ALL,while age(≥10 years),initially diagnosed WBC count(≥50×109/L),M3 bone marrow on day 15,and MRD-positive at week 12 were the independent risk factors due to treatment failure.No secondary tumors were found during the follow-up for 10 years.Conclusion:Relapse is the main cause of treatment failure in children with ALL.The initially diagnosed WBC count,immunophenotype and MRD at week 12 were the independent prognostic factors for relapse of the patients.Financial burden accounts for a large proportion of non-relapse death.