Following allogeneic hematopoietic stem cell transplantation (alloHSCT), children are at risk of life-threatening pneumococcal infections. Whereas vaccination with polysaccharide vaccines fails to elicit protective immunity in most alloHSC transplant recipients, pneumococcal conjugate vaccines may effectively prevent invasive disease by eliciting T-cell-dependent antibody responses. Here, we report safety and immunogenicity in 53 children immunized with a regimen of 3 consecutive doses of a heptavalent pneumococcal conjugate vaccine (7vPCV) in monthly intervals starting 6 to 9 months after alloHSCT. Immunization was well tolerated with no vaccine-related serious adverse events. Serologic IntroductionPatients following allogeneic hematopoietic stem cell transplantation (alloHSCT) are at significant risk of life-threatening infections despite leukocyte engraftment. 1,2 This is based on the loss of protective immunity to vaccine-preventable diseases and the relative immaturity of the emerging immune system. [3][4][5][6][7][8][9] In this setting, infections with encapsulated bacteria, particularly pneumococci, are associated with significant rates of morbidity and mortality. 10,11 Epidemiologic studies have shown a cumulative incidence of invasive pneumococcal disease between 1% and 10% with a median onset at 1 year following transplantation. 12,13 Therefore, effective prevention, including chemoprophylaxis and active immunization, is warranted. This is particularly true for children who on reintegration into day care and school become highly exposed to pathogens. Current guidelines of the Centers for Disease Control and Prevention (CDC) and the European Blood and Marrow Transplantation group (EBMT) generally recommend vaccination of all alloHSC transplant recipients with the standard 23-valent pneumococcal polysaccharide vaccine starting at 12 months after transplantation. 14,15 Because of immaturity of the immune system, however, vaccination with polysaccharide vaccines fails to elicit protective immunity in the majority of pediatric alloHSC transplant recipients, with response rates ranging from 20% to 30% in the first to 50% in the second year after alloHSCT. 16,17 In contrast, in the heptavalent pneumococcal conjugate vaccine (7vPCV), serotypespecific polysaccharides are conjugated to an immunogenic protein carrier and hence elicit T-cell-dependent antibody responses. 7vPCV contains the 7 most prevalent pneumococcal serotypes and The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. For personal use only. on May 12, 2018. by guest www.bloodjournal.org From provides effective protection against invasive disease in infants and young children who, like alloHSC transplant recipients, only weakly respond to polysaccharide vaccines as a result of immunologic immaturity. [18][19][20] Currently,...

Recipients of allogeneic hematopoietic stem cell transplantion (alloHSCT) lose protective immunity to vaccine-preventable disease and thus are at increased risk of developing infections, in particular with encapsulated bacteria such as pneumococci and Haemophilus influenzae. However, several important issues on reimmunization after alloHSCT remain unresolved due to the lack of clinical studies especially in the pediatric setting. Here we report the results of the prospective, multicenter vaccination trial IKAST (NCT 00169728) and show for the first time that coadministration of the hexavalent tetanus, diphtheria, acellular pertussis, poliomyelitis, Haemophilus influenzae type B and hepatitis B combination vaccine Infanrix hexa™ (6vCV; GlaxoSmithKline Pharma) along with the heptavalent pneumococcal conjugate vaccine Prevenar™ (PCV7; Wyeth Pharma) provides early protective antibody responses against a broad range of vaccine antigens in the vast majority of pediatric HSCT recipients. Following alloHSCT from related (n=37) or unrelated (n=40) donors a total of 77 children (median age 8.3 (1.4–17.0) years) were immunized with a primary series of three monthly doses of 6vCV in conjunction with PCV7 starting as early as 6 months after transplantation irrespective of immunosuppressive therapy and graft-versus-host-disease, with a subsequent booster dose at 18 months. Immunogenicity was analysed by assessment of antibody concentrations, adverse events were monitored by a standardized diary and physician’s assessment. Prior to vaccination only 8.2% and 12.8% of patients exhibited protective antibodies towards 6vCV and PCV7 vaccine antigens, respectively. As a result of a highly significant increase in mean antibody concentrations (p<0.001) protection to all 6vCV and PCV7 vaccine antigens was achieved in 85.1% and 89.8% of patients after primary immunization within the 1st year after alloHSCT, and this was independent of patient age, donor type, in vitro/in vivo T cell depletion, stem cell source, and conditioning (p>0.05). Although nine months later, prior to booster vaccination, 63.8% and 83.7% of patients retained protective antibody levels, mean antibody concentrations had dropped by a factor of 1.9–4.8 (p<0.001) except for one pneumococcal serotype, underlining the need for subsequent vaccination. Following booster immunization, antibody concentrations increased 2.4-19.1 fold (p<0.001) indicating robust memory responses, and 100% and 91.5% of patients achieved protective antibody levels against all 6vCV and PCV7 antigens, respectively. Vaccination was generally well tolerated with no vaccine-related serious adverse events. Our data show that early immunization of pediatric alloHSCT recipients according to our simple and convenient revaccination schedule is safe and provides early and comprehensive vaccination coverage during the first 2 years following stem cell transplantation.