伴CREBBP基因突变的儿童急性淋巴细胞白血病14例临床分析

Childhood acute lymphoblastic leukemia with CREBBP gene mutation: a clinical analysis of 14 cases

摘要:

目的 探讨伴CREBBP基因突变的儿童急性淋巴细胞白血病（acute lymphoblastic leukemia, ALL）的临床特征及预后。方法 回顾性分析2016年1月—2023年12月郑州大学第一附属医院儿童医院收治的14例初诊伴CREBBP基因突变的ALL患儿的临床资料。结果 伴CREBBP基因突变的ALL患儿占同期确诊ALL患儿的1.5%（14/963），其中男4例（29%），女10例（71%），中位诊断年龄为4岁3.5个月。免疫学分型均为B-ALL，均合并其他类型基因突变，包括NRAS、KRAS、ETV6、FLT3、PAX5、SH2B3、CDKN2A和CDKN2B，且有4例染色体核型异常。14例患儿均采用VDLP方案诱导治疗，第1个疗程完全缓解（complete remission, CR）率为79%（11/14）。3例患儿发生单纯骨髓复发，复发率为21%（3/14），1例应用贝林妥欧单抗治疗后达CR，余2例行复发方案化疗后桥接造血干细胞移植。1例患儿因中断治疗死亡，余13例均无病存活。5年总生存率为92%±7%，无事件生存率为73%±13%。结论 伴CREBBP基因突变的初诊儿童ALL多见于女性，诱导缓解率低，复发率高，常伴其他类型基因突变和异常染色体核型。大部分复发患儿采用免疫治疗或行造血干细胞移植后仍可获得长期存活。

Abstract:

Objective To investigate the clinical features and prognosis of childhood acute lymphoblastic leukemia (ALL) with CREBBP gene mutation.Methods A retrospective analysis was performed for the clinical data of 14 ALL children with CREBBP gene mutation who were admitted to Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023.Results The ALL patients with CREBBP gene mutation accounted for 1.5% (14/963) among all children diagnosed with ALL during the same period of time, among whom there were 4 boys (29%) and 10 girls (71%), with a median age of 4 years and 3.5 months. All children had an immunological type of B-cell ALL and concurrent mutations in other genes including NRAS, KRAS, ETV6, FLT3, PAX5, SH2B3, CDKN2A, and CDKN2B, and 4 children had karyotype abnormality. All 14 children received induction therapy with the VDLP regimen, with a complete remission (CR) rate of 79% (11/14) after the first course of treatment. Three children experienced bone marrow recurrence alone, with a recurrence rate of 21% (3/14), among whom 1 child achieved CR after blinatumomab therapy and 2 received bridging hematopoietic stem cell transplantation after chemotherapy for recurrence. Among the 14 children, 1 died due to treatment discontinuation and 13 achieved disease-free survival. The 5-year overall survival rate was 92%±7%, and the event-free survival rate was 73%±13%.Conclusions ALL with CREBBP gene mutation is more common in girls and has a low induction remission rate and a high recurrence rate, and it is often accompanied by other types of gene mutations and abnormal karyotypes. Most children with recurrence can achieve long-term survival after immunotherapy or hematopoietic stem cell transplantation.