Abstract
Background: Chronic myeloid leukemia (CML) is driven by the BCR-ABL1 fusion oncoprotein and is usually controllable with first- and second-generation tyrosine-kinase inhibitors (TKIs). However, ~5–7 % of patients eventually develop blast crisis, and a minority of these transform to B cell acute lymphoblastic leukemia (ALL-B), a biologically aggressive state with a median overall survival of only 6–12 months despite therapy. Third-generation TKIs such as ponatinib, as well as antibody-based or cellular therapies (e.g., blinatumomab, inotuzumab ozogamicin, CAR-T), are emerging as potential options for refractory lymphoid blast crisis.
Case presentation: A 38-year-old man with a 10-year history of CML on sequential imatinib then nilotinib presented with progressive fatigue, bleeding, and fever. Laboratory studies demonstrated leukocytosis with 86% blasts, severe anemia, and thrombocytopenia. Bone-marrow examination confirmed lymphoid transformation; flow cytometry revealed CD34+CD19+CD79a+ blasts with aberrant CD13/CD33. BCR-ABL1-kinase domain sequencing showed no T315I mutation, yet clinical resistance to both TKIs was evident. Cytoreduction with hydroxyurea provided transient benefit. Given poor performance status and infection risk, LALA chemotherapy was proposed as a tolerable, stem cell transplant–bridging regimen; however, the patient elected for home-based palliative care and died one week after discharge.
Conclusion: CML transformation to ALL-B poses formidable diagnostic and therapeutic challenges and carries a dismal prognosis with a less than 20% five-year survival. LALA chemotherapy may be a reasonable option in patients who are clinically vulnerable or immunocompromised. Timely recognition of disease transformation and early referral for potentially curative interventions such as stem cell transplantation are essential in managing high-risk CML. Future directions include integrating ponatinib or other novel TKIs with immunotherapeutic approaches to improve outcomes in lymphoid blast crisis.
Keywords
Chronic myeloid leukemia, Blast crisis, B cell acute lymphoblastic leukemia, Byrosine kinase inhibitor resistance, LALA chemotherapy