Administration of intravenous immunoglobulin in patients with chronic lymphocytic leukemia and infectious complications
Authors: Horodyska T.O. , Lukavetsky L.M. , Tsyapka O.M. , Pelenyo N.V. , Kotlyarchuk K.B. , Simonova M.I. , Boyko O.I. , Tkhir Kh.R. , Maslyak Z.V. 
Published: October 2020

Background. Chronic lymphocytic leukemia (CLL) is one of the most frequent malignant blood disorders in adult patients. For the last several decades treatment of CLL made its way from simple chemotherapy agents (chlorambucil, cyclophosphamide, fludarabine) to highly technological innovative medications (monoclonal antibodies, targeted agents, CAR T-cell therapy). Despite quite high rate of remissions induced by the novel treatment methods significant proportion of the patients develop infectious mostly bacterial complications in the long term. Various infections often become the cause of mortality in CLL patients in remission. They develop in about 70 % of the patients and become severe in about 30 % of them (requiring inpatient hospitalization and/or intravenous antibacterial treatment). Novel agents for treatment of CLL influencing the immune B-cells lead to immune suppression (secondary hypogammaglobulinemia, immunoglobulin G (IgG) deficiency), distribution and severity of infectious complications. Substitutive treatment with intravenous IgG changed clinical course of the secondary hypoimmunoglobulinemia reducing significantly incidence of the infectious events in CLL patients as well as in patients undergoing immunochemotherapy (ICT) and immunosuppressive treatment.

Objective. To determine the necessity for immunocorrection in patients with CLL requiring ICT.

Materials and methods. Patients with the diagnosis of CLL undergoing ICT within hematology department developing infectious complications were observed.

Results and discussion. Patients with CLL undergoing ICT were tested and analyzed and according to the results in 31 of these patients hypogammaglobulinemia and reduced levels of IgG were revealed. In 8 of the patients reduction of IgG was detected already at the primary diagnosis of CLL (Binet stages B and C). Depending on the performed treatment of CLL frequency of infectious complications differed and was the highest in subjects with progressive course of leukemia and in those who were treated with RFC (rituximab, fludarabine and cyclophosphamide) ICT. Levels of IgG ranged from 0.86 to 5.55 g/L (median – 3.49 g/L, lower-upper quartile – 2.62-4.76 g/L). Levels of hypogammaglobulinemia in the whole group ranged from 4.49 to 16.87 g/L (median – 12.11 g/L, lower-upper quartile – 11.44-12.88 g/L). Patients underwent the substitutive treatment with intravenous immunoglobulin with the dose of 0.4 g/kg every month. The medication was administered according to standard recommendations. There were no side effects registered within 24 h of infusion. Additionally, patients with infectious complications were treated with antibacterial, antifungal and antiviral agents. After application of intravenous immunoglobulin general condition of the patients improved, body temperature normalization and reduction of recurrent infectious events were observed. The mean time from the diagnosis of persistent hypogammaglobulinemia to complete resolution of infectious complications was 12.5 months (ranging from 3.6 to 27 months). Our results suggested that patients with IgG deficiency without signs of infection responded better to this treatment. Levels of IgG increased from 6.57 to 13.5 g/L (median – 9.35 g/L, lower-upper quartile – 7.57-10.70 g/L) and levels of γ-globulin grew from 14.4 to 17.69 g/L (median – 16.70 g/L, lower-upper quartile – 15.96-17.30 g/L).

Conclusions. Secondary hypogammaglobulinemia and deficiency of the serum IgG often develop in patients with blood malignancies, especially in those involving clonal proliferation of the B-cells, like in CLL. According to our study immunocorrection by intravenous immunoglobulin resulted in resolution of infectious complications in all cases of confirmed immunodeficiency. In order to prevent severe infections in CLL patients it is expedient to perform screening of the humoral immunity status before initiation of ICT and in case of development of febrile conditions.