Tyrosine Kinase Inhibitor Treatment of a Patient with Chronic Myeloid Leukemia and Congenital Thrombophilia.

Background and Clinical Significance: Chronic Myeloid Leukemia (CML) management has been revolutionized by tyrosine kinase inhibitors (TKIs), though cardiovascular and thrombotic complications remain a concern, especially in patients with underlying risk factors. Inherited thrombophilia, including protein S deficiency and Factor V Leiden mutation, poses a substantial risk for venous thromboembolism (VTE). Managing CML in patients with such prothrombotic predispositions presents complex therapeutic challenges, particularly in selecting an appropriate TKI and managing anticoagulation. Case Presentation: A 33-year-old woman with congenital thrombophilia (type I protein S deficiency and heterozygous Factor V Leiden mutation) and a history of VTE on long-term anticoagulation with acenocoumarol presented with CML. She exhibited primary resistance to first-line imatinib and poor tolerance with suboptimal response to second-line bosutinib. Third-line treatment with asciminib led to a rapid and sustained major molecular response (MR4.5) without bleeding or thrombotic complications.

Conclusions

This case highlights the importance of individualized, multidisciplinary management in CML patients with coexisting thrombophilia. Asciminib, with its favorable cardiovascular safety profile, represents a promising therapeutic option in high-risk patients where other TKIs may be contraindicated due to resistance, intolerance, or thrombotic risk.