Vaccine Reponses Following Unmodified or T Cell Depleted Unrelated and Mismatched Related HCT.
Authors: Small Trudy N. , Papadopoulos Esperanza B. , Boulad Farid , Kernan Nancy A. , Ford Ruth , Taylor Joanne , Casson Anne , Torok-Castanza Joann , Cuello Bernadette , Young James W. , Jakubowksi Ann , Castro-Malaspina Hugo , Perales Miguel , O’Reilly Richard J. 
Published: October 2019

Abstract
Infection continues to contribute to morbidity and mortality late after hematopoietic stem cell transplant (HCT). The development of evidence-based guidelines for immunizing patients post HCT could substantially reduce this risk, particularly in view of the severity of many vaccine preventable infections in the naïve unimmunized host. The efficacy of current vaccine strategies, including the CDC guidelines, have not been tested in large numbers of patients, particularly following unrelated or HLA-mismatched related HCT. We retrospectively analyzed the pre and post vaccine titers of 103 patients transplanted from an unrelated (n=83) or HLA-mismatched (MM) donor (n=20) between 1/1/92 and 2/1/03. Thirty-three percent of the unrelated grafts were unmodified. The remainder were T cell depleted (TCD)using soybean agglutination followed by rosetting with sheep red blood cells (78%), CD34 selection followed by rosetting with sheep red blood cells (12%), or partial TCD using MoAb (12%). Of the 20 HLA-MM related grafts, 13 were TCD (SBA-E- BM, n=4, CD34+E-PBSC (n=9). Adults (>18 years) comprised 43 and 30% of the unrelated and MM-related groups, respectively. Patients were vaccinated according to guidelines recommended for previously unimmunized children, with the exception of live viral vaccines. Rather than vaccination at fixed times post transplant, the majority of patients were vaccinated when their CD4 cell counts were >200/ul and their T cell response to PHA was >75% of normal. Recipients of an unrelated or MM-related transplant were re-immunized starting a median (range) of 442 and 509 days post transplant, respectively. Seroconversion following a series of 3 tetanus and IPV vaccinations occurred in over 90% of patients regardless of transplant type. Following primary immunization with conjugated Haemophilus influenza B (Hib) vaccine, 21% of MM-related and 15% of unrelated HCT recipients failed to develop positive titers despite a series of 3 vaccinations. Sixty-six percent of MM-related and 75% of unrelated transplant recipients seroconverted following 3 recombinant HepB vaccinations. Less than 40% of unrelated transplant recipients responded to the 23-valent polysaccharide pneumococcal vaccine despite administration at a median of 2.5 years post transplant. In contrast 68% seroconverted following three immunizations with the 7-valent protein conjugated pneumococcal vaccine given 2 months apart. The majority of patients did not however seroconvert after only one dose of the 7-valent conjugated pneumococcal vaccine. Forty-six patients received an MMR vaccine. No unexpected toxicities were observed despite failure in 30 and 50% of unrelated and HLA-mismatched related transplant recipients, respectively. This data suggests that current immunization guidelines which recommend vaccination of all transplant recipients at fixed times post transplant (12 and 24 months) may not have adequately factored in the prolonged and variable immunodeficiency observed in unrelated and mis-matched related transplant recipients, that primary immunization against pneumococcus should consist of a series of the 7-valent conjugated pneumococcal vaccine, and that assessment of pre and post vaccination titers is essential to ensure protection against vaccine preventable diseases.