Morbidity and Mortality Associated with Development of Hypogammaglobulinemia after Rituximab

*Corresponding author: Hitoshi Hanamoto*, Aki Fujii, Mariko Fujita, Ko Fujimoto and Ryosuke Fujiwara

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retrospective study



Low-levels of gamma globulin are associated with a risk of infection, and complications of hypogammaglobulinemia are often observed in hematologic malignancies. In chronic lymphocytic leukemia (CLL), IgG≀600 mg/dL is reportedly associated with higher risks of infection. The objective was to determine the risks of hypogammaglobulinemia and infection in malignant lymphomas for which rituximab that targets B-cells is used.


A retrospective analysis of data from medical records of patients with malignant lymphomas treated with rituximab-containing therapy at our hospital between April 2014 and March 2016 was performed to assess the risks of infections through an evaluation of IgG levels and hospitalizations for and deaths due to infections in patients hospitalized with infections during this period.


From April 2014 to March 2016, 128 patients with malignant lymphomas received rituximab-containing therapy at our hospital, and 94 (61%) of these patients had IgG levels measured. These 94 patients were included in the analysis. The histological types were as follows: 30 had follicular lymphoma (FL), 17 had indolent non-Hodgkin’s lymphoma (iNHL), 42 had diffuse large B-cell lymphoma (DLBCL), and 5 had mantle cell lymphoma (MCL). The mean minimum immunoglobulin G (IgG) level in patients hospitalized for infection was 546 mg/dL and was 628 mg/dL in those not hospitalized (p=0.6). Although a significant difference was not observed, IgG levels tended to be low in hospitalized patients with infection. In addition, there were 4 patients with mean IgG levels that were 600 mg/dL or less in the 6-months immediately prior to hospitalization. Among these 2 died of infection.


Low-levels of gamma globulin are associated with a risk of mortality due to infections in malignant lymphomas.


Hypogammaglobulinemia; Malignant lymphoma; Rituximab.


CLL: Chronic lymphocytic leukemia; FL: Follicular lymphoma; iNHL: Indolent non-Hodgkin’s lymphoma; DLBCL: Diffuse large B-cell lymphoma; MCL: Mantle cell lymphoma; FN: Febrile neutropenia.