CCCG-ALL-2015方案治疗儿童急性淋巴细胞白血病复发的危险因素分析

Risk factors for recurrence of childhood acute lymphoblastic leukemia after treatment with the Chinese Children's Cancer Group ALL-2015 protocol

摘要:

目的 分析儿童急性淋巴细胞白血病（acute lymphoblastic leukemia, ALL）经中国儿童肿瘤协作组急性淋巴细胞白血病2015方案（Chinese Children's Cancer Group ALL-2015 protocol, CCCG-ALL-2015）治疗后的累积复发率（cumulative incidence of relapse, CIR），并探讨影响复发的危险因素。方法 回顾性分析2015年1月—2019年12月接受CCCG-ALL-2015方案治疗的852例患儿的临床资料，计算CIR并分析影响儿童急性B淋巴细胞白血病（B-ALL）复发的危险因素。结果 852例ALL患儿中，146例（17.1%）发生复发，8年CIR为（19.8±1.6）%。B-ALL与急性T淋巴细胞白血病患儿的8年CIR比较差异无统计学意义（P>0.05）。146例复发患儿中，复发时间主要集中于极早期（62例，42.5%）和早期（46例，31.5%），极早期单纯骨髓复发42例（28.8%），早期单纯骨髓复发27例（18.5%）。Cox比例风险回归模型分析显示，融合基因MLLr阳性（HR=4.177，95%CI：2.086~8.364，P<0.001）和第46天微小残留病≥0.01%（HR=2.013，95%CI：1.163~3.483，P=0.012）是B-ALL患儿经CCCG-ALL-2015方案治疗后复发的危险因素。结论 儿童ALL经CCCG-ALL-2015方案治疗后仍有较高的复发率，以极早期和早期单纯骨髓复发常见；第46天微小残留病≥0.01%、融合基因MLLr阳性与B-ALL复发密切相关。

Abstract:

Objective To investigate the cumulative incidence of recurrence (CIR) in children with acute lymphoblastic leukemia (ALL) after treatment with the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol and the risk factors for recurrence.Methods A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019. CIR was calculated, and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia (B-ALL) were analyzed.Results Among the 852 children with ALL, 146 (17.1%) experienced recurrence, with an 8-year CIR of 19.8%±1.6%. There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group (P>0.05). For the 146 children with recurrence, recurrence was mainly observed in the very early stage (n=62, 42.5%) and the early stage (n=46, 31.5%), and there were 42 children with bone marrow recurrence alone (28.8%) in the very early stage and 27 children with bone marrow recurrence alone (18.5%) in the early stage. The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene (HR=4.177, 95%CI: 2.086-8.364, P<0.001) and minimal residual disease≥0.01% on day 46 (HR=2.013, 95%CI: 1.163-3.483, P=0.012) were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol.Conclusions There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol, mainly bone marrow recurrence alone in the very early stage and the early stage, and minimal residual disease≥0.01% on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.