Mercaptopurine-induced secondary aplastic anemia in an acute lymphoblastic leuke-mic child with dihomozygous TPMT*3C and NUDT15 c.415 mutations:a case report and literature review
Objective To enhance the clinical awareness regarding the myelosuppression induced by mercap-topurine(6-MP)leading to secondary aplastic anemia under specific genetic polymorphisms(mutations in TPMT and NUDT15),in order to reduce the risk of such adverse reactions.Methods A retrospective analysis was conducted on a case of an acute lymphoblastic leukemia pediatric patient with dihomozygous mutations of 6-MP metabolic genes TPMT*3C and NUDT15 c.415 who developed aplastic anemia following 6-MP treatment.The relationship between the occurrence of secondary aplastic anemia and 6-MP use,as well as its association with TPMT and NUDT15 gene mu-tation was further explored through a comprehensive review of domestic and foreign literature.Results The patient developed a fever and experienced a reduction in white blood cells,neutrophils,platelets counts,and reticulocyte ratio 7 days after receiving the initial dose of 6-MP(40 mg/m2).Genetic testing revealed homozygous mutations for TPMT*3C CC and NUDT15 c.415 TT.Bone marrow biopsy indicated decreased hematopoietic function,leading to a diagno-sis of secondary aplastic anemia.Following symptomatic treatment,blinatumomab was used as a bridge to allogeneic hematopoietic stem cell transplantation,with a favorable outcome.6-MP was not used again in subsequent treatments.There have been no prior reports,either domestically or internationally,of patients carrying homozygous mutations in both TPMT and NUDT15.Conclusion Mutations in TPMT and NUDT15 genes can lead to abnormal metabolism of thiopurines.Therefore,it is recommended to conduct relevant genetic testing before 6-MP treatment and adjust the initial dose of the drug based on the test results to minimize the risk of severe adverse reactions such as myelosuppression.
万方数据
维普
