Abstract

BackgroundChronic lymphocytic leukemia (CLL) leads to significant immune system dysfunction. The predominant clinical presentation in 50% of patients involves recurrent, often severe, infections. Infections are also the most common (60–80%) cause of deaths in CLL patients. The scope of infections varies with the clinical stage of the disease. Treatment-naive patients typically present with respiratory tract infections caused by encapsulated bacteria Streptococcus pneumoniae and Haemophilus influenzae. Since 2012, the 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended in the United States and some EU countries for pneumococcal infection prevention in patients with CLL (besides the long-standing standard, 23-valent pneumococcal polysaccharide vaccine, PPV23). The aim of this study was to compare the immune response to PCV13 in 24 previously untreated CLL patients and healthy subjects.MethodsBoth groups were evaluated for: the levels of specific pneumococcal antibodies, the levels of IgG and IgG subclasses and selected peripheral blood lymphocyte subpopulations including the frequency of plasmablasts before and after immunization.ResultsAdequate response to vaccination, defined as an at least two-fold increase in specific pneumococcal antibody titers versus pre-vaccination baseline titers, was found in 58.3% of CLL patients and 100% of healthy subjects. Both the CLL group and the control group demonstrated a statistically significant increase in the IgG2 subclass levels following vaccination (P = 0.0301). After vaccination, the frequency of plasmablasts was significantly lower (P<0.0001) in CLL patients in comparison to that in controls. Patients who responded to vaccination had lower clinical stage of CLL as well as higher total IgG, and IgG2 subclass levels. No significant vaccine-related side effects were observed.ConclusionsPCV13 vaccination in CLL patients is safe and induces an effective immune response in a considerable proportion of patients. To achieve an optimal vaccination response, the administration of PCV13 is recommended as soon as possible following CLL diagnosis.

Highlights

  • Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in European and North American adult populations leading to significant immune system dysfunction [1]

  • Adequate response to vaccination was defined as an at least two-fold increase in specific pneumococcal antibody titers versus pre-vaccination baseline titers. This vaccination response criterion was achieved by 100% of subjects from the control group and 58.3% of CLL patients

  • The specific pneumococcal antibody titers following PCV13 vaccination were significantly higher in the control group versus the CLL group (P50.037)

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Summary

Introduction

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in European and North American adult populations leading to significant immune system dysfunction [1]. The dominant clinical presentation in 50% patients are recurrent, often severe, infections [2,3,4]. The first-line treatment recommended for CLL patients in good general condition with no significant comorbidities is immunochemotherapy with purine analogue fludarabine combined with cyclophosphamide and rituximab (FCR regimen) [8]. Results: Adequate response to vaccination, defined as an at least two-fold increase in specific pneumococcal antibody titers versus pre-vaccination baseline titers, was found in 58.3% of CLL patients and 100% of healthy subjects. Both the CLL group and the control group demonstrated a statistically significant increase in PLOS ONE | DOI:10.1371/journal.pone.0114966. Both the CLL group and the control group demonstrated a statistically significant increase in PLOS ONE | DOI:10.1371/journal.pone.0114966 December 15, 2014

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