title: Immunogenicity, safety, and tolerability of 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine in recipients of allogeneic hematopoietic stem cell transplant aged ≥2 years: an open-label study.
abstract: BACKGROUND
  Life-threatening Streptococcus pneumoniae infections often occur after hematopoietic stem cell transplant (HSCT); vaccination is important for prevention.
  
  
  METHODS
  In an open-label study, patients (n = 251) 3-6 months after allogeneic HSCT received 3 doses of 13-valent pneumococcal conjugate vaccine (PCV13) at 1-month intervals, a fourth dose 6 months later, and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) 1 month later. Immunogenicity at prespecified time points and vaccine safety were assessed.
  
  
  RESULTS
  In the evaluable immunogenicity population (N = 216; mean age, 37.8 years), geometric mean fold rises (GMFRs) of immunoglobulin G geometric mean concentrations from baseline to postdose 3 showed significant increases in antibody levels across all PCV13 serotypes (GMFR range, 2.99-23.85; 95% confidence interval lower limit, >1); there were significant declines over the next 6 months, significant increases from predose 4 to postdose 4 (GMFR range, 3.00-6.97), and little change after PPSV23 (GMFR range, 0.86-1.12). Local and systemic reactions were more frequent after dose 4. Six patients experienced serious adverse events possibly related to PCV13 (facial diplegia, injection-site erythema and pyrexia, autoimmune hemolytic anemia, and suspected lack of vaccine efficacy after dose 3 leading to pneumococcal infection), PCV13 and PPSV23 (Guillain-Barré syndrome), or PPSV23 (cellulitis). There were 14 deaths, none related to study vaccines.
  
  
  CONCLUSIONS
  A 3-dose PCV13 regimen followed by a booster dose may be required to protect against pneumococcal disease in HSCT recipients. Dose 4 was associated with increased local and systemic reactions, but the overall safety profile of a 4-dose regimen was considered acceptable.
  
  
  BACKGROUND
  NCT00980655.
authors: Hopital Henri Mondor, Assistance Publique-Hopitaux de Paris, and Université Paris-Est-Créteil, France.
authors: Catherine
authors: C
authors: Cordonnier
authors: Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors: Per
authors: P
authors: Ljungman
authors: Pfizer Pharma GmbH, Berlin, Germany.
authors: Christine
authors: C
authors: Juergens
authors: Universitaire Ziekenhuizen Gasthuisberg, Leuven.
authors: Johan
authors: J
authors: Maertens
authors: AZ Sint-Jan Brugge-Oostende, Belgium.
authors: Dominik
authors: D
authors: Selleslag
authors: inVentiv Health Clinical, LLC, Princeton, New Jersey.
authors: Vani
authors: V
authors: Sundaraiyer
authors: Pfizer Inc, Pearl River, New York;
authors: Peter C
authors: PC
authors: Giardina
authors: Pfizer Inc, Surrey, United Kingdom.
authors: Keri
authors: K
authors: Clarke
authors: Pfizer Inc, Pearl River, New York;
authors: William C
authors: WC
authors: Gruber
authors: Pfizer Inc, Pearl River, New York;
authors: Daniel A
authors: DA
authors: Scott
authors: Pfizer Pharma GmbH, Berlin, Germany.
authors: Beate
authors: B
authors: Schmoele-Thoma
mesh_terms: D000293:Adolescent; D000907:Antibodies, Bacterial / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000706:statistics & numerical data*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000009:adverse effects* / Q000276:immunology*
chemical_list: C538862:13-valent pneumococcal vaccine; C414006:23-valent pneumococcal capsular polysaccharide vaccine; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines
keywords: 13-valent pneumococcal conjugate vaccine; 23-valent pneumococcal polysaccharide vaccine; Streptococcus pneumoniae infections; hematopoietic stem cell transplant