Tumor Lysis Syndrome Triggered by Acalabrutinib in Chronic Lymphocytic Leukemia (CLL): Diagnostic and Therapeutic Implications

Tumor lysis syndrome (TLS) is an uncommon but potentially life-threatening oncologic emergency, typically associated with highly proliferative hematologic malignancies. It is rarely encountered in chronic lymphocytic leukemia (CLL), a generally indolent B-cell neoplasm. We report a unique case of therapy-induced TLS in a patient newly diagnosed with CLL, following the initiation of acalabrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. The patient presented with marked hyperleukocytosis, severe thrombocytopenia, and acute kidney injury at diagnosis. Immunophenotyping and histopathological evaluation confirmed the diagnosis of CLL, supported by a Matutes score of 4/5 and characteristic CD5+/CD23+/weak CD20 expression. Cytogenetic analysis revealed no high-risk abnormalities. Following acalabrutinib initiation, the patient rapidly developed metabolic disturbances, including severe hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, and worsening renal function, consistent with laboratory and clinical TLS. Prompt management with intravenous hydration, Rasburicase, calcium supplementation, and potassium-lowering agents led to gradual metabolic correction. This case highlights the importance of recognizing the potential for TLS even in slow-growing hematologic malignancies like CLL, especially in patients with high tumor burden or compromised renal function. Clinicians must maintain a high index of suspicion and initiate appropriate prophylactic measures when starting targeted therapies, particularly BTK inhibitors, to prevent life-threatening complications.