Severe bone marrow aplasia following azathioprine therapy in patients with NUDT15 deficiency: A case series

Azathioprine is widely used in various autoimmune disorders, hematological malignancies, inflammatory bowel disease, skin disorders, and in post renal transplants as an immunosuppressant. Myelosuppression is a well-known adverse drug reaction related to thiopurines including azathioprine, 6-mercaptopurine, and thioguanine. Thiopurine S-methyltransferase (TPMT) and Nudix hydrolase 15 ( NUDT15 ) are two critical enzymes involved in metabolism of azathioprine and other thiopurines. Genetic polymorphism affects enzyme activity, and thus metabolism of these drugs (Azathioprine, 6-mercatopurine, and thiogunine). People with enzyme deficiency are at increased risk of prolonged and severe myelosuppression following treatment with azathioprine and other thiopurine drugs. Loss-of-function alleles in the NUDT15 gene are reported to be common than TPMT in south Asian population. Here, we are reporting six cases of NDUT15 polymorphism that was admitted in our institute. Retrospective data were collected from the January 2024 to June 2024 of patients who were admitted at our institute. We also reviewed PubMed data base for literature on NUDT15 polymorphism in south Asian population. In conclusion, NUDT15 polymorphism is more prevalent in south Asian population, and thus, testing for NUDT15 polymorphism could help to individualize thiopurine therapy better in the South Asian population and should be done in the patients who experience severe myelosuppression following introduction of azathioprine and other thiopurines.