Optimizing therapy in chronic myeloid leukemia with resistance and severe systemic manifestations

Abstract

This case highlights the complexity of tyrosine kinase inhibitor (TKI) resistance in patients with advanced chronic myeloid leukemia (CML), requiring an integrated and multidisciplinary diagnostic and therapeutic approach. The progression of CML does not always conform to standard protocols, particularly when TKI resistance leads to progressive systemic manifestations. We describe the case of a 44-year-old woman with CML who developed TKI resistance (T315I mutation and increasing BCR-ABL1 IS values) after receiving imatinib and nilotinib. This patient experienced several severe systemic complications, including progressive pericardial and bilateral pleural effusions, splenomegaly, ascites, cholestasis, and sepsis due to Staphylococcus aureus infection. These manifestations presented significant challenges in management. The complexity of this case necessitated aggressive and targeted infection management. A therapy transition to ponatinib emerged as a more promising option given the confirmed TKI resistance. This case study underscores that optimal management of CML with TKI resistance and multi-system involvement requires a comprehensive multidisciplinary approach, integrating infection control, management of systemic complications, and strategic optimization of CML therapy holistically. Timely therapy transition is crucial for overcoming TKI intolerance and suboptimal response.