异基因造血干细胞移植治疗TP53突变合并髓系恶性转化的SDS 1例报道并文献复习

Allogeneic hematopoietic stem cell transplantation for myeloid malignancies secondary to Shwachman-Diamond syndrome with TP53 mutation:A case report and literature review

目的:探讨TP53突变合并髓系恶性转化的Shwachman-Diamond综合征(Shwachman-Diamond syndrome,SDS)患者的病例特征及治疗方案,提高对该病的认识。方法:通过检索知网、PubMed、Web of Science和Embase数据库中有关TP53突变合并髓系恶性转化的SDS患者的相关文献,总结归纳此类患者的病例特征、治疗过程与预后,分析了1例明确诊断为TP53突变合并AML-MR的SDS患儿的诊治经过。结果:本例SDS患儿血液系统方面主要表现为全血细胞减少,随着年龄的增长,发生MDS转化,最终进展为AML-MR,体细胞获得性TP53突变可能是其发生髓系恶性转化的驱动因子。异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,Allo-HSCT)是此类患者的唯一治愈方式,本例患儿在移植前选择阿扎胞苷(Azacitidine,AZA)联合维奈克拉(Venetoclax,VEN)进行桥接及时控制疾病进展,低强度骨髓预处理方案提升预后,术后恢复良好,然而移植一年后因疾病快速进展而去世。既往报道的10例经过移植的同类患者均未取得良好疗效和预后。结论:TP53突变是本例SDS患儿发生髓系恶性转化的早期驱动因子,且可能在晚期进展中也发挥着驱动作用。在Allo-HSCT前后选择合适的处理方案可能是提高TP53突变合并髓系恶性转化的SDS患者移植预后的潜在方式。此外,提升对本病的认识及进行及时监测,在发生恶性转化之前进行移植也有助于提升本病的预后。

Objective:To investigate the case characteristics and treatment of Shwachman-Diamond syndrome(SDS)patients with TP53 mutation and myeloid malignancies transformation,and to improve the understanding of the disease.Methods:By searching the relevant literature on SDS patients with TP53 mutation combined with myeloid malignancies transformation in CNKI,PubMed,Web of Science and Embase databases,the case characteristics,treatment process and prognosis of such patients were summarized.The diagnosis and treatment process of a SDS patient diagnosed as TP53 mutation combined with AML-MR were analyzed.Results:The hematological system of this case of SDS was mainly characterized by pancytopenia.With the increase of age,myelodysplastic syndrome(MDS)transformation occurred and eventually progressed to AML-MR.Somatic cell-acquired TP53 mutation may be the driving factor for its malignant transformation of myeloid system.Allogeneic hematopoietic stem cell transplantation(Allo-HSCT)is the only cure for this type of patient.In this case,the patient chose Azacitidine(AZA)combined with Veneolax(VEN)for bridging and timely control of disease progression before transplantation.The low-intensity bone marrow pre-treatment regimen improved prognosis and resulted in good postoperative recovery.However,one year after transplantation,the patient passed away due to rapid disease progression.The 10 cases of similar patients who have been transplanted have not achieved good curative effect and prognosis.Conclusion:TP53 mutation is an early driver of myeloid malignancies transformation in this case of SDS,and may also play a driving role in late progression.Choosing the appropriate treatment before and after Allo-HSCT may be a potential way to improve the prognosis of SDS patients with TP53 mutation and myeloid malignancies transformation.In addition,improving the understanding of the disease and timely monitoring,transplantation before malignant transformation can greatly improve the prognosis of the disease.