Coadministration of the Hexavalent Combination Vaccine Infanrix hexa™ and the Pneumoccoccal Conjugate Vaccine Prevenar™ Provides Early and Comprehensive Vaccination Coverage in Children after Related and Unrelated Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Meisel Roland , Kuypers Lisa , Gruhn Bernd , Strauss Gabi , Strahm Brigitte , Ehlert Karoline , Beutel Karin , Holter Wolfgang , Bluetters-Sawatzki Renate , Feuchtinger Tobias , Gruettner Hans-Peter , Schubert Ralf , Diedrich Sabine , Riffelmann Marion , Laws Hans-Juergen , Dilloo Dagmar 
Published: April 2020

Abstract
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&lt;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&gt;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&lt;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&lt;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.