Safety and Immunogenicity of the 13-Valent Protein-Conjugated Pneumococcal Vaccine(PCV13) Following Related and Unrelated Hematopoietic Stem Cell Transplantation (HCT)
Authors: Small Trudy N , Jakubowski Ann A. , Barker Juliet N , Kernan Nancy A. , Prockop Susan E , Iovino Christine Scura , Nicole LeStrange , Perales Miguel-Angel , Castro-Malaspina Hugo , Koehne Guenther , Giralt Sergio , Papadopoulos Esperanza B 
Published: October 2019

Abstract
Abstract 3037
In 2009, the Center for International Blood and Marrow Transplant Research (CIBMTR) published an updated, unified international set of post HCT vaccine guidelines which for the first time recommended vaccinating all patients with the protein conjugated pneumococcal vaccine (PCV7), rather than the pure polysaccharide vaccine PPV23, which is poorly immunogenic in this patient population. Due to the licensing of PCV13 in 2010 and cessation of PCV7 production, the guidelines were updated in 2010 to substitute PCV13 for PCV7. To date, there are limited studies evaluating PCV13 in HCT recipients. Since May of 2010, 59 patients transplanted at this center received three doses of PCV13 administered 1–3 months apart following an HLA-matched sibling (n=17) or alternative donor (n=42) HCT. The median patient age (range) at HCT was 39 (range: 3–68) years. The majority of patients were transplanted for acute leukemia (63%) or myelodysplastic syndrome (15%). Thirty-three percent of patients received an unmodified graft. Due to the variable kinetics of immune reconstitution post HCT in recipients of alternative donor HCTs compared to HLA matched siblings, patients were immunized upon acquisition of minimal milestones of immune competence (CD4 cell count >200 cells/ul and IgG level >500 mg/dl at least 6 weeks off gammaglobulin), rather than at fixed times post HCT. The median time to vaccination was 452 (range: 143–1187) days post HCT. Time to vaccination was significantly shorter in patients <21 versus >21 years of age (median: 318 vs 498 days, p=0.006) and significantly longer in patients who received post HCT rituximab versus those who did not (median: 610 versus 405 days, p=<0.001). Response was defined as seroconversion or 3 fold rise in titer against serotypes 1, 3, 4, 14, 19, 23, 26, 51, and 56. There were no serious adverse events attributable to the vaccine. Prior to immunization, 77% of patients were susceptible to >7 measured serotypes. Overall response was 73%, including 87% of patients <21 years of age at HCT and 67% of adults. Poorer responses were observed in recipients of post HCT rituximab despite a median CD19 cell count of 342 /ul at the time of vaccination. Response correlated with higher levels of circulating CD4+CD45RA+ T cells/ul (p=0.03) and CD27+, IgM- (memory isotype switched) B cells/ul, (p=0.03). This study suggests that PCV13 is very immunogenic when given upon acquisition of pre-set immune milestones. Results of an ongoing international trial in which PCV13 is initiated 3–6 months post HCT will determine its immunogenicity when given early post HCT. Prospective trials designed to identify biological markers predictive of an optimal and durable PCV13 response are needed.

Disclosures:
Small: Pfizer, Inc: Equity Ownership, family member employed by Pfizer, Inc. Off Label Use: Use of 13cPnC in transplant patients. Perales:Pfizer, Inc: Equity Ownership.