Distinct clinical associations of baseline and treatment-emergent hypogammaglobulinemia in diffuse large B-cell lymphoma: a retrospective real-world cohort study
- 1Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Akdeniz University, Antalya, 07100 Turkey
- 2Faculty of Medicine, Department of Internal Medicine, Akdeniz University, Antalya, 07100 Turkey
- 3Department of Internal Medicine, Finike State Hospital, Antalya, 07100 Turkey
Abstract
Hypogammaglobulinemia is increasingly recognized in B-cell malignancies, but whether its clinical significance differs by timing, present at diagnosis versus developing after treatment, remains unclear in diffuse large B-cell lymphoma (DLBCL). We retrospectively evaluated 181 adults with newly diagnosed DLBCL treated with rituximab-based immunochemotherapy at a tertiary referral center. Hypogammaglobulinemia was defined as serum IgG < 7 g/L and classified as baseline hypogammaglobulinemia (BHG), treatment-emergent hypogammaglobulinemia (TEHG), or absent. Among the study population, 107 patients (59.1%) developed hypogammaglobulinemia, including 30 (16.6%) with BHG and 77 (42.5%) with TEHG. Patients with BHG exhibited a more adverse baseline clinical profile characterized by poorer performance status and higher-risk disease features. Complete response rates differed significantly across groups and were lowest in patients with BHG (73.3%) compared with TEHG (88.3%) and no hypogammaglobulinemia (94.6%) (p = 0.008). BHG was also associated with the poorest survival outcomes, with median progression-free survival (PFS) and overall survival (OS) of 26.4 and 30.9 months, respectively. In multivariable analyses, BHG independently predicted infectious complications but was not an independent predictor of PFS. TEHG was associated with shorter PFS in the primary multivariable model; however, this association was not confirmed in a prespecified 6-month landmark analysis. These findings suggest that BHG and TEHG represent distinct clinical states in DLBCL. While BHG identifies a clinically vulnerable subgroup with increased infection risk and inferior outcomes, the prognostic significance of TEHG should be interpreted cautiously because of non-protocolized monitoring and potential ascertainment bias.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00277-026-07169-9.
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BibTeX
@article{iltar2026distinct,
title = {{Distinct clinical associations of baseline and treatment-emergent hypogammaglobulinemia in diffuse large B-cell lymphoma: a retrospective real-world cohort study}},
author = {Utku Iltar and Tugba Karacamli and Sinem Oztekin and Unal Atas and Ece Vural and Orhan Kemal Yucel and Ozan Salim and Levent Undar},
journal = {Annals of Hematology},
year = {2026},
month = jul,
doi = {10.1007/s00277-026-07169-9},
url = {https://doi.org/10.1007/s00277-026-07169-9},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Distinct clinical associations of baseline and treatment-emergent hypogammaglobulinemia in diffuse large B-cell lymphoma: a retrospective real-world cohort study
AU - Utku Iltar
AU - Tugba Karacamli
AU - Sinem Oztekin
AU - Unal Atas
AU - Ece Vural
AU - Orhan Kemal Yucel
AU - Ozan Salim
AU - Levent Undar
PY - 2026
DA - 2026/07/30
JO - Annals of Hematology
DO - 10.1007/s00277-026-07169-9
UR - https://doi.org/10.1007/s00277-026-07169-9
AB - Hypogammaglobulinemia is increasingly recognized in B-cell malignancies, but whether its clinical significance differs by timing, present at diagnosis versus developing after treatment, remains unclear in diffuse large B-cell lymphoma (DLBCL). We retrospectively evaluated 181 adults with newly diagnosed DLBCL treated with rituximab-based immunochemotherapy at a tertiary referral center. Hypogammaglobulinemia was defined as serum IgG < 7 g/L and classified as baseline hypogammaglobulinemia (BHG), treatment-emergent hypogammaglobulinemia (TEHG), or absent. Among the study population, 107 patients (59.1%) developed hypogammaglobulinemia, including 30 (16.6%) with BHG and 77 (42.5%) with TEHG. Patients with BHG exhibited a more adverse baseline clinical profile characterized by poorer performance status and higher-risk disease features. Complete response rates differed significantly across groups and were lowest in patients with BHG (73.3%) compared with TEHG (88.3%) and no hypogammaglobulinemia (94.6%) (p = 0.008). BHG was also associated with the poorest survival outcomes, with median progression-free survival (PFS) and overall survival (OS) of 26.4 and 30.9 months, respectively. In multivariable analyses, BHG independently predicted infectious complications but was not an independent predictor of PFS. TEHG was associated with shorter PFS in the primary multivariable model; however, this association was not confirmed in a prespecified 6-month landmark analysis. These findings suggest that BHG and TEHG represent distinct clinical states in DLBCL. While BHG identifies a clinically vulnerable subgroup with increased infection risk and inferior outcomes, the prognostic significance of TEHG should be interpreted cautiously because of non-protocolized monitoring and potential ascertainment bias. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00277-026-07169-9.
SN - 0939-5555
SN - 1432-0584
ER -