Pretreatment immunoglobulin profiles and survival outcomes in hematologic malignancies and autoimmune cytopenias: a comparative cohort analysis.

[BACKGROUND] Alterations in immunoglobulin levels are commonly observed in hematologic malignancies and immune-mediated cytopenias, reflecting underlying immune dysregulation. While the prognostic relevance of hypogammaglobulinemia (HGG) has been studied in chronic lymphocytic leukemia (CLL), comparable data across a broader range of hematologic diagnoses remain limited. This study aimed to conduct a comparative analysis of baseline immunoglobulin profiles (IgG, IgA, IgM, IgE) across a heterogeneous cohort of patients with NHL, CLL, HL, ITP, and AIHA. Our primary objective was to evaluate the disease-specific associations of these profiles with survival outcomes to identify diagnostic groups that benefit most from baseline immune profiling.

[RESULTS] A total of 779 patients were included: 294 with NHL, 220 with CLL, 106 with HL, 128 with ITP, and 31 with AIHA. Quantitative and categorical analyses demonstrated significant differences in immunoglobulin levels across disease groups. CLL patients exhibited the highest frequency of low immunoglobulin levels, particularly for IgM and IgA. Kaplan–Meier analysis revealed numerically shorter overall survival in patients with low pretreatment IgG levels, although this difference was not statistically significant in the pooled heterogeneous cohort ( = 0.119). However, this association was not confirmed in the overall multivariable Cox regression model. Subgroup analysis using diagnosis-specific Cox models identified normal/high IgG status as independently associated with improved survival in NHL (HR: 0.543;  = 0.017), but not in CLL, HL, ITP, or AIHA. Associations for IgA, IgM, and IgE with mortality were not evaluated in these diagnosis-specific models.

[CONCLUSIONS] While low pretreatment IgG levels were associated with poorer survival in the overall cohort on univariate analysis, this association was not significant in the multivariable model. However, subgroup analysis identified low IgG as an independent and significant predictor of mortality in patients with NHL, but not in other diagnoses. These findings highlight that the prognostic value of immunoglobulin profiling is highly disease-specific. Baseline IgG assessment appears most relevant for risk stratification in NHL. However, the use of all-cause mortality limits our ability to discern the specific mechanism (e.g., infection-related vs. disease-progression-related) underlying this association.