A Randomized, Double-Blind Trial of Pneumococcal Vaccination in Adult Allogeneic Stem Cell Transplant Donors and Recipients

Transplant Infectious Diseases, University of Alberta, Edmonton, Alberta, Canada.
Clinical Infectious Diseases (Impact Factor: 8.89). 01/2008; 45(12):1576-82. DOI: 10.1086/523583
Source: PubMed


Adult allogeneic hematopoietic stem cell transplant (HSCT) recipients are at high risk of invasive pneumococcal disease but have suboptimal responses to the recommended pneumococcal polysaccharide vaccine (PPV23). Pneumococcal conjugate vaccine (PCV7) may improve immunogenicity in this population, and a donor vaccination strategy may benefit patients undergoing HSCT.
Sixty-four pairs of donors and recipients scheduled to undergo HSCT were randomized to receive either PPV23 or PCV7. Vaccinations were administered to donors before transplantation and to recipients at 6 months after transplantation. Serotype-specific antipneumococcal titers were measured in donors at the time of harvest and in recipients before transplantation and 6 and 12 months after transplantation.
Overall, immunogenicity was poor with both strategies. However, at 6 months, response to at least 1 serotype was seen in 0 (0%) of 19 and 8 (38.6%) of 21 evaluable recipients whose donors had received PPV23 and PCV7, respectively (P=.003). At 12 months, response was seen in 10 (55.6%) of 18 and 20 (90.9%) of 22 HSCT recipients who had received PPV23 and PCV7, respectively (P=.02). Multivariate logistic regression revealed that, at 12 months after transplantation, the type of vaccine given was the only significant factor affecting response, with an odds ratio of 8.85 (95% confidence interval, 1.62-47.6; P=.012) favoring PCV7.
A donor and recipient paired vaccination strategy with PCV7 demonstrated safety and greater immunogenicity than did a similar strategy with PPV23.

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    • "The advantage of conjugate over polysaccharide formulations is that the former induce protective circulating antibodies and establish polysaccharide-specific (PS) B cell memory associated with longterm protection against pneumococcus in healthy children older than 2 years. In contrast, in subjects with underlying medical conditions , the kinetics of immune response to 7-valent pneumococcal conjugate vaccine (PCV7) revealed rapid antibody decline following initial immunization [5] [6]. "
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    ABSTRACT: Safety and immunogenicity of a booster dose of 7-valent pneumococcal conjugate vaccine (PCV7) were evaluated in 29 patients with idiopathic nephrotic syndrome (INS), who had been primed 12 months earlier with one dose of PCV7. PCV7 was not associated with increased risk of INS relapse (RR=0.77, p=0.8) and serotype-specific antibodies increased in all subjects at 1 month (p<0.01). The quantitative characteristics of immune response and the effect of treatment with mycophenolate mofetil and/or cyclosporine A following booster PCV7 were similar with primary response. Additional PCV7 doses could be safely given in children with INS to increase circulating antibodies above the protective threshold.
    Vaccine 01/2014; 32(12). DOI:10.1016/j.vaccine.2013.11.106 · 3.62 Impact Factor
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    • "However, this study could not confirm the superiority of single-dose vaccination with PCV7 over PPV. Kumar et al. reported slightly better immune responses (defined as a Ptwofold antibody titer increase and an absolute titer of P0.35 lg/ml) in allogeneic hematopoietic stem cell transplant recipients who had received PCV7 six months after transplantation compared to those who received PPV [34]. The cited vaccination regimen was preceded by vaccination of the healthy stem cell donors with the same vaccine types before transplantation , which makes comparisons difficult. "
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    ABSTRACT: Background Vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV) has been recommended for elderly patients with B cell malignancies and dysfunctions because of their enhanced susceptibility to pneumococcal infections. More recent recommendations advocate the use of conjugate pneumococcal vaccines. Methods We compared responses to single dose vaccination with either PPV or the 7-valent pneumococcal conjugate vaccine (PCV7) in fifty-six patients ⩾60 years with a diagnosis of multiple myeloma (n = 24), Waldenstrom’s macroglobulinemia (n = 15) and the non-malignant B cell disorder monoclonal gammopathy of undetermined significance (MGUS) (n = 17), and 20 age-matched controls. Serum was collected prior to vaccination and 4–8 weeks later, and analyzed for IgG antibody levels to pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F by ELISA. Functional antibody activity towards pneumococcal serotypes 4 and 14 was measured using an opsonophagocytic killing assay (OPA). Results All patient groups had lower pre-vaccination IgG antibody and OPA titers to the investigated serotypes compared to the healthy controls. Following vaccination, myeloma patients responded with significant IgG titer increases to 1/7 serotypes and OPA titer increases to 1/2 serotypes. Corresponding IgG and OPA vaccine responses were 3/7 and 0/2 for Waldenstrom patients, 4/7 and 1/2 for MGUS patients, and 4/7 and 2/2 for the healthy controls, respectively. Notably high antibody levels without corresponding OPA titers were seen among a few myeloma patients indicating the presence of non-functional antibodies. Neither of the two vaccines elicited significantly higher serotype-specific IgG concentrations, OPA titers or antibody fold increases in any of the study groups. Hypogammaglobulinemia and ongoing chemotherapy were associated with poor vaccine responses in a multivariate analysis. Conclusion Our findings confirm that B cell malignancies and disorders among elderly patients are associated with suboptimal responses to pneumococcal vaccination. Single-dose PCV7 was not shown to be superior to PPV.
    Trials in Vaccinology 12/2013; 2(1). DOI:10.1016/j.trivac.2013.09.001
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    • "Pneumococcal infections are among the most important causes of morbidity and mortality after allogeneic SCT because of functional hyposplenism or decreased production of Streptococcus pneumoniae-specific opsonizing antibodies as a result of pre-conditioning regimens, incomplete immune reconstitution, and/or chronic GVHD [5, 6, 21-24]. Epidemiological studies have shown that invasive pneumococcal disease occurs in 590 out of 100,000 and 199 out of 100,000 allogeneic and autologous SCT cases per year, respectively, compared with 11.5 out of 100,000 age-matched controls [25]. "
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    ABSTRACT: Antibody titers to vaccine-preventable diseases such as tetanus, polio, measles, mumps, and rubella decline within 1-10 years after allogeneic or autologous hematopoietic stem cell transplantation (SCT) if the recipient is not vaccinated. Vaccine-preventable diseases such as pneumococcal diseases, Haemophilus influenzae type b infections, influenza, measles, and varicella can pose an increased risk for SCT recipients. Therefore, after SCT, the recipients should be routinely revaccinated. Vaccination recommendations have previously been developed and published by the European Group of Blood and Marrow Transplantation and the Centers for Disease Control, by the Infectious Diseases Society of America, and by the American Society for Blood and Marrow Transplantation in 2009. Different epidemiologies and strategies have existed in Korea. In 2012, the Korean Society of Infectious Diseases published "Vaccination for Adult" describing the guidelines for vaccination, one of the chapters assigned for vaccination of SCT recipients. The present article reviews the current available vaccination strategies for SCT recipients, their family members, and healthcare workers, with the focus on recent Korean perspectives.
    09/2013; 45(3):272-282. DOI:10.3947/ic.2013.45.3.272
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