From Solid Organ Malignancies to Dual Leukaemias: Sequential CLL and CML in a Cancer Survivor.

Introduction: Chronic lymphocytic leukaemia (CLL), the most common adult leukaemia is known to undergo Richter's transformation. However, transformation into myeloid neoplasms is extremely rare with no established pathogenetic mechanisms. Management of coexisting haematological neoplasms becomes more complex in the presence of prior solid organ malignancies, potential therapy-related complications, and immunosuppression. Case description: An 83-year-old man with prior history of invasive bladder cancer (s/p chemotherapy and cystectomy in 2013) and pancreatic adenocarcinoma treated with Whipple's procedure in 2015 was diagnosed with CLL in 2015 without 17p deletion. He began treatment with Ibrutinib in 2018 due to bulky symptomatic adenopathy and later switched to acalabrutinib due to arthralgias. Following a hospitalization in 2022 for coronavirus disease 2019, he was found to have chronic myeloid leukaemia (CML), confirmed by BCR-ABL positivity and bone marrow biopsy. Imatinib was started for CML but due to potential drug-induced pulmonary toxicity, switched to asciminib. His BCR-ABL transcript was undetectable, and therapy was discontinued due to multiple hospitalizations with organizing pneumonia. His course was further complicated by neutropenic fever and hypogammaglobulinemia and he transitioned to hospice care for better quality of life. Thus, both CLL and CML were treated with targeted oral agents. Conclusion: This report highlights concurrent CLL and CML in a patient with multiple prior malignancies treated with chemotherapy and surgical interventions. It also adds to the limited literature on the CLL to CML overlap, suggesting vigilant long-term surveillance in cancer survivors. Coexisting management of haematological malignancies need careful weighing of individual toxicity profiles of medications tailored to individual patient. LEARNING POINTS: Chronic lymphocytic leukaemia (CLL) most commonly transforms into aggressive lymphoma; development of chronic myeloid leukaemia (CML) in a patient with CLL should prompt evaluation for an independent myeloid clone rather than presumed transformation.Myeloid neoplasms in patients with CLL may arise from therapy-related leukemogenesis or divergent evolution from a shared hematopoietic progenitor, highlighting the importance of molecular characterization.Management of coexisting CLL and CML requires individualized risk-benefit assessment, particularly in elderly patients with prior solid tumours and immune dysfunction.