Randomized study of early versus late immunization with pneumococcal conjugate vaccine after allogeneic stem cell transplantation.
BACKGROUND
Invasive pneumococcal disease is a life-threatening complication after allogeneic stem cell transplantation, and at least 20% of cases occur within 1 year after transplantation. The 23-valent pneumococcal polysaccharide vaccine (PPV23) has limited efficacy, especially during the first year after transplantation. The immune response to the conjugated vaccines is expected to be better than that to the polysaccharide vaccine, but the optimal timing of vaccination is not defined. Our objective was to show that a 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) was not inferior when first given 3 months after transplantation, compared with when first given 9 months after transplantation.


METHODS
We performed a multicenter, randomized, noninferiority study involving 158 patients from 13 European Group for Blood and Marrow Transplantation centers who were randomly allocated at approximately 100 days after myeloablative stem cell transplantation to receive a series of vaccinations (3 doses of PCV7 given 1 month apart) that was started immediately (i.e., 3 months after transplantation) or 6 months later (i.e., 9 months after transplantation). The primary evaluation criterion was the rate of response (antibody level, > or = 0.15 microg/mL for each of the 7 serotypes) at 1 month after the third dose of PCV7. The noninferiority margin was 20%. All patients were followed up for 24 months after transplantation or until death, whichever occurred first.


RESULTS
We found that the response rate was not lower after early vaccination (79% [45 of 57 patients]) than after late vaccination (82% [47 of 57 patients]) (difference, -3.5%; 90% confidence interval, -15.6 to 8.6; not significant).


CONCLUSIONS
We conclude that PCV7 vaccination at 3 months after stem cell transplantation is not inferior to PCV7 vaccination at 9 months after transplantation. Because invasive pneumococcal disease can occur early, we recommend starting the PCV7 vaccination series at 3 months after transplantation to ensure earlier protection against Streptococcus pneumoniae. However, the early vaccination may result in only short-lasting response and may not prime for a 23-valent pneumococcal polysaccharide vaccine boost as efficiently as the late vaccination.
Cordonnier
Catherine
C
Hematology Department, Henri Mondor Teaching Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP) and Paris 12 University, Créteil, France. carlcord@club-internet.fr
Labopin
Myriam
M
Chesnel
Virginie
V
Ribaud
Patricia
P
De La Camara
Rafael
R
Martino
Rodrigo
R
Ullmann
Andrew J
AJ
Parkkali
Terttu
T
Locasciulli
Anna
A
Yakouben
Karima
K
Pauksens
Karlis
K
Einsele
Hermann
H
Niederwieser
Dietger
D
Apperley
Jane
J
Ljungman
Per
P
D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D002648:Child; D005060:Europe; D005260:Female; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D033581:Stem Cell Transplantation; D013997:Time Factors; D055815:Young Adult
D000907:Antibodies, Bacterial; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D007166:Immunosuppressive Agents; D022242:Pneumococcal Vaccines