Background and importance 6-mercaptopurine (6-MP) is an anticancer and immunosuppressive agent used as part of the therapeutic strategy in acute lymphoblastic leukaemia (ALL), in the induction, consolidation and maintenance phases. However, it may cause life threatening myelotoxicity that is commonly associated with polymorphisms in genes involved in its metabolism (thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15)).

Aim and objectives To describe the clinical case of a Caucasian girl, aged 2 years, diagnosed with B-ALL (intermediate risk of hyperdiploidy in cytogenetics (DNI index 1.27) and MRD on day +15 of 1.4%, CNS-1) that presented prolonged myelotoxicity under the LAL-SEHOP-PETHEMA-2013 treatment protocol.

Material and methods During the induction phase, prolonged spinal cord aplasia occurred with the complication of sepsis due to Staphylococcus epidermidis, which required intensive care unit support. Subsequently, she presented sepsis due to Pseudomonas, a granuloma in the reservoir area that requires channelling of a peripheral access central catheter type PICC. TPMT polymorphisms (*2, *3A, *3B and *3C) were studied without alterations. Therefore, the consolidation phase continued, and she presented with aplasia, febrile neutropenia, respiratory infection and central venous catheter infection. The dose of 6-MP was reduced to 10%. In the reinduction phase she also showed aplasia, febrile neutropenia and mucocutaneous infection by Candida dubliniensis. During maintenance, methotrexate and 6-MP were suspended several times, and 6-MP was resumed at 3% of the dose. She received multiple transfusions of red blood cells and platelets.

To understand the toxicity manifested by the patient and considering the update of the pharmacogenetic guide for thiopurines of the Clinical Pharmacogenetics Implementation Consortium, real time PCR genotyping by Taqman was performed for NUDT15-rs116855232 gene polymorphism.

Results Although initial genetic testing revealed that the patient carried the TPMT wild-type allele, the patient had prolonged spinal cord aplasia and multiple infectious complications. Subsequent analysis revealed that the patient carried the rs116855232-TT genotype (frequency in Europeans 0.000004). This polymorphism is associated with potentially fatal myelosuppression (evidence level 1A), which explains the toxicity manifested.

Conclusion and relevance This case shows the relevance of implementing pharmacogenetics studies (TPMT and NUDT15 gene polymorphisms) in daily clinical practice that allows the early detection of patients treated with 6-MP with a higher risk of myelosuppression.

Conflict of interest No conflict of interest