The Electrolyte Storm as an Early Indicator of Cytokine Release and Tumor Lysis in Treatment-Naïve Chronic Myeloid Leukemia: A Retrospective Correlative Analysis

Abstract

Background: In treatment-naïve chronic-phase chronic myeloid leukemia (CML), subclinical cytokine release and tumor lysis may precede overt metabolic complications, yet early, accessible biomarkers remain undefined . Objective: To determine whether concurrent hyponatremia and hyperkalemia—termed “Electrolyte Storm”—are independently associated with inflammatory (ferritin, IL‑6) and lytic (LDH, blood urea) markers after adjusting for renal function. Patients and Methods: This retrospective correlational study included 150 treatment‑naïve adults with chronic‑phase CML. Hyponatremia (Na⁺ <135 mmol/L), hyperkalemia (K⁺ >5.2 mmol/L), and Electrolyte Storm (both) were predefined. IL‑6, IL‑1β, and antidiuretic hormone were measured. Multivariate regression, Spearman correlations, and sensitivity analysis (excluding creatinine >1.2 mg/dL) were applied . Results: Hyponatremia occurred in 32.0% (48/150), hyperkalemia in 44.7% (67/150), and Electrolyte Storm in 18.0% (27/150). Sodium correlated inversely with ferritin (ρ = –0.52, p<0.001) and IL‑6 (ρ = –0.48, p<0.001). Potassium correlated positively with LDH (β = 0.49, p<0.001) and blood urea (β = 0.31, p<0.001), but not with creatinine (p=0.38). The Electrolyte Storm group showed markedly higher LDH (378.5 vs. 264.2 U/L), ferritin (498.5 vs. 312.3 ng/mL), and IL‑1β (12.3 vs. 5.6 pg/mL) (all p<0.01). All associations remained significant after excluding patients with renal impairment (n=130). Conclusion: The Electrolyte Storm phenotype serves as an early, low‑cost surrogate for underlying cytokine release and tumor lysis in untreated CML, independent of kidney dysfunction. Clinically, hyponatremia should raise suspicion of paraneoplastic inflammation rather than simple volume depletion, while disproportionate hyperkalemia signals high lytic burden. Routine electrolyte panels may aid in risk stratification before initiating tyrosine kinase inhibitors.