Tyrosine kinase inhibitor resistance: a case report on chronic myeloid leukemia and Gilbert's syndrome.

Although tyrosine kinase inhibitors (TKI) are commonly used as targeted treatment options for chronic myeloid leukemia (CML), its use is associated to UGT1A1 polymorphisms and, consequently, are related to a higher risk of manifesting Gilbert's syndrome, a genetic disorder associated to hyperbilirubinemia. The report of concomitant condition of CML and Gilbert's Syndrome is uncommon. Therefore, the aim of this study was to report the clinical case of a patient diagnosed with CML and subsequently, with Gilbert's Syndrome. A 34-year-old female was diagnosed with CML. On physical examination, spleen and liver were palpable, indicating hepatosplenomegaly. Laboratory findings of peripheral blood showed leukocytosis (165,190/mm3), 6% of blasts and a bone marrow biopsy showed hypercellularity by granulocytic series with moderate maturation delay. After diagnosis, the patient immediately started chemotherapy with the TKI Imatinib. One year after treatment, due to the partial response, the therapy was changed to Nilotinib, resulting in a complete response. Despite the absence of hyperbilirubinemia, a genetic study by polymerase chain reaction (PCR) verified a positivity for Gilbert's Syndrome. TKIs are also inhibitors of the enzyme UDPGT1, leading to deficient glucuronidation, causing manifestation of Gilbert's Syndrome. This report demonstrates the case of a patient that, besides having two coexisting conditions that could cause hyperbilirubinemia, did not have bilirubin alterations and it highlights the importance of having genetic investigations in cancer patients, in order to identify secondary diseases that could worsen the course of treatment. 2021 AME Case Reports. All rights reserved.