Association Between the Systemic Immune-Inflammation Index and Overall Survival in Patients With Leukemia: A Multicenter Cohort Study

Background: The systemic immune-inflammation index (SII; platelet × neutrophil / lymphocyte) is a well-established prognostic marker in solid tumors, but its clinical significance in leukemia remains unclear, where peripheral blood cytopenias may primarily reflect bone marrow failure rather than conventional cancer-related inflammation.

Methods: We retrospectively analyzed 609 leukemia patients from a multicenter registry, split into training (n=427) and validation (n=182) cohorts. Baseline SII was calculated before therapy. A data-derived SII threshold was identified in the training cohort using maximally selected rank statistics. Overall survival was assessed using Kaplan–Meier curves, Cox regression, and restricted cubic splines. A nomogram was constructed based on the multivariable Cox model and internally evaluated using bootstrap calibration for 1- and 3-year survival.

Results: An SII cutoff of 173.56 significantly separated survival (log-rank P<0.001). After adjustment for the demographic, comorbidity, and treatment variables available in the registry, higher SII (≥173.56) remained associated with a lower hazard of death (hazard ratio [HR] = 0.41; 95% confidence interval [CI], 0.31–0.55; P < 0.001). Spline analyses suggested a nonlinear inverse association between SII and mortality. The nomogram showed acceptable internal calibration in both cohorts.

Conclusions: Higher baseline SII was consistently associated with better overall survival in this multicenter leukemia cohort. This association may reflect differences in underlying disease burden and preserved hematopoietic function, rather than an independent biological effect of SII. Because leukemia subtype, disease status, and cytogenetic and molecular risk were unavailable, whether SII adds prognostic value beyond established leukemia risk factors remains uncertain. These findings support further evaluation of SII in well-characterized, subtype-specific cohorts.