Phase-specific impact of hypogammaglobulinemia on bacterial infections after allogeneic hematopoietic cell transplantation.

Infections are a major complication after allogeneic hematopoietic cell transplantation (allo-HCT). Although humoral immunity is essential, the phase-specific role of IgG remains unclear. We analyzed 579 allo-HCT recipients, stratified into early, intermediate, and late post-transplant phases. The incidence of bacterial infections during the intermediate phase decreased with increasing IgG trough levels (incidence rate ratio [IRR], 0.85; 95% confidence interval [CI]: 0.78-0.94, p < 0.01), whereas no association was observed in the early or late phases. During the intermediate phase, multivariable analyses demonstrated that hypogammaglobulinemia (IRR, 1.70; 95% CI: 1.11-2.62, p = 0.02) and acute graft-versus-host disease with grade II-IV (IRR, 2.10; 95% CI: 1.39-3.18, p < 0.01) were associated with bacterial infections. In models including high-dose steroid exposure, steroid therapy was independently associated with bacterial infections, whereas the effect of hypogammaglobulinemia was attenuated. There was a trend toward an interaction between hypogammaglobulinemia and high-dose steroid exposure. A stratified analysis suggested that hypogammaglobulinemia had a more pronounced impact among patients without high-dose steroids (IRR 1.86; 95% CI: 1.09-3.16; p = 0.02). These findings suggest the clinical relevance of hypogammaglobulinemia is phase-specific and influenced by the intensity of immunosuppressive therapy. Monitoring IgG during this period may help identify candidates for targeted immunoglobulin replacement therapy.