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Conjugated Pneumococcal Vaccine Triggers a Better Immune Response than Polysaccharide Pneumococcal Vaccine in Patients with Chronic Lymphocytic Leukemia - A Randomized Study by the Swedish CLL group
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Aim: To determine if patients with untreated chronic lymphocytic leukemia (CLL) benefit from vaccination with a 13-valent conjugated pneumococcal vaccine (PCV13), Prevenar13®, compared with a 23-valent capsular polysaccharide vaccine (PPSV23), Pneumovax®, in terms of immune response.

 

Background: Patients with CLL have an increased risk for infection and Streptococcus pneumoniae is one of the most common pathogens with high morbidity.  Patients with CLL are known to respond poorly to the traditionally used polysaccharide vaccines. Conjugation of polysaccharide to protein carriers renders a thymus-dependent, memory-inducing and more immunogenic vaccine. In patients with CLL, there is no consensus on a recommendation for pneumococcal vaccination, due to a lack of comparative studies.

 

Methods: 128 treatment naïve CLL patients from eight hematology clinics in Sweden were randomized to vaccination with PCV13 (n=63) or PPSV23 (n=65) after stratification by IgG levels and CLL clinical stage (Rai). Blood samples for evaluation of immune response were obtained at baseline, at one and at six months after vaccination. Analyses for each of the 12 pneumococcal serotypes common for PCV13 and PPSV23 were performed by opsonophagocytic assay (OPA) and enzyme-linked immunosorbent assay (ELISA).

 

Results: PCV13 elicited a superior immune response than PPSV23 in 10/12 serotypes one month after vaccination and in 5/12 serotypes six months after vaccination, measured as OPA geometric mean titers (GMTs). Geometric mean concentrations of serotype-specific IgG antibodies elicited by PCV13 as measured by ELISA, were higher than those elicited by PPSV23 in half of the common serotypes, both after one and six months. The proportion of patients with good response (defined as response in 8 of 12 common serotypes according to predefined response criteria) was higher in PCV13 recipients than in PPSV23 recipients after one month (40% vs. 22%, p=0.034) as well as after six months (33% vs. 17%, p=0.041). Never did PPSV23 trigger a better immune response for any of the serotypes, than PCV13, regardless of analysis. For two of the serotypes, OPA GMTs were lower at the six months than at the one-month follow up. Negative predictive factors for vaccination response were hypogammaglobulinemia and long disease duration. Both vaccines were well tolerated.

 

Conclusions: In patients with previously untreated CLL, the efficacy of PCV13 in terms of immune response is superior to PPSV23 for many serotypes common for the two vaccines. PCV13 should be considered as a part in vaccination programs against Streptococcus pneumoniae for these patients and administered as early as possible during the course of the disease. 

Keyword [en]
Chronic lymphocytic leukemia (CLL), vaccine, Pneumococci, Pneumococcal vaccine, Polysaccharide vaccine, protein-conjugate vaccine, immunogenicity
National Category
Medical and Health Sciences
Research subject
Oncology
Identifiers
URN: urn:nbn:se:uu:diva-316457OAI: oai:DiVA.org:uu-316457DiVA: diva2:1077872
Available from: 2017-03-01 Created: 2017-03-01 Last updated: 2017-03-01
In thesis
1. Infectious and bleeding complications in patients with hematological malignancies: Studies on diagnosis and prevention
Open this publication in new window or tab >>Infectious and bleeding complications in patients with hematological malignancies: Studies on diagnosis and prevention
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The overall aim of this thesis is to improve knowledge about the prevention of infectious and bleeding complications in patients with hematological malignancies, primarily in those with chronic lymphocytic leukemia (CLL) and myelodysplatic syndrome (MDS).

Hypogammaglobulinemia, impaired production of immunoglobulins (Ig), is an established risk factor for infection, but the impact of IgG pure subclass deficiency (IgG subclass deficiency with adequate production of IgG, IgA, and IgM) has been debated. In a retrospective single institution study, we concluded that pure IgG subclass deficiency in CLL patients is rare and is not associated with an increased risk of infection. Hence, routine analysis of IgG subclasses in patients with CLL is not warranted.

There is no consensus on recommending vaccination against Streptococcus pneumoniae to CLL patients mainly because comparative studies are lacking. In our randomized trial, the efficacy of a conjugated pneumococcal vaccine on immune response was superior or equal to a polysaccharide vaccine for all pneumococcal serotypes common for the two vaccines. A conjugate pneumococcal vaccine should therefore be included in vaccination programs for patients with CLL.

Bronchoalveolar lavage (BAL) is a well-established invasive method to identify the cause of pulmonary infiltrates in immunocompromised patients. In a retrospective trial, we have studied the diagnostic yield of BAL in patients with hematological malignancies. We concluded that BAL is highly useful in either verifying or excluding some of the important respiratory tract infections affecting these patients, particularly invasive pulmonary aspergillosis (IPA) and Pneumocystis jirovecii pneumonia (PJP). However, standardized procedures for BAL sampling should be continually revised to avoid unnecessary microbiological tests.

Thrombocytopenia, an adverse prognostic factor in patients with MDS, can be aggravated by azacitidine, first-line treatment for high-risk MDS. Eltrombopag, a thrombopoietin-receptor agonist (TPO-R), alleviates thrombocytopenia in patients with immune thrombocytopenic purpura (ITP). In a phase I clinical trial, we concluded that the combination of eltrombopag and azacitidine in high-risk MDS patients with thrombocytopenia is feasible and well tolerated in doses up to 200 mg eltrombopag daily.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 49 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1304
Keyword
Chronic lymphocytic leukemia, Immunodeficiency, Hypogammaglobulinemia, IgG subclass, Pneumococci, Pneumococcal vaccine, Polysaccharide vaccine, Protein-conjugate vaccine, Aspergillosis, Bronchoalveolar lavage, Invasive fungal disease, Pneumocystis jirovecii pneumonia, Myelodysplastic syndrome, Azacitidine, Eltrombopag, Thrombocytopenia, Thrombopoietin receptor
National Category
Medical and Health Sciences
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-316461 (URN)978-91-554-9830-6 (ISBN)
Public defence
2017-04-24, Rosénsalen, Akademiska sjukhuset, Ingång 95/96 nbv, Sjukhusvägen, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2017-04-03 Created: 2017-03-01 Last updated: 2017-04-18

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