Use of the Tetanus Toxoid, Reduced Dose Diphtheria and Pertussis Vaccine (Tdap) in Allogeneic Transplant (alloHCT) Recipients.

The incidence of pertussis in the United States has steadily increased over the last decade particularly in adolescents and adults. In 2005, in an effort to reduce pertussis in these populations, two vaccines containing tetanus, reduced diphtheria and pertussis toxoids (Tdap) were approved. The two Tdap vaccines contained the same amount of tetanus toxoid (TT) but differ in the amount of diphtheria and pertussis toxoid per dose as well as their indicated age range. In 2006, the Advisory Committee on Immunization Practices recommended that all adolescents and adults receive a single dose of Tdap. Currently, there are limited data on the immunonogenicity of these vaccines in alloHCT patients. Since 2005, 64 alloHCT recipients have received Tdap at our center. The vaccine administered is approved for individuals 11 to 64 yrs of age and contained 2.5 ug of pertussis toxoid (PT), 2.5 Lf diphtheria toxin, and 5 Lf tetanus toxoid (TT) per dose. The median age at HCT was 19 years. The median age (range) at vaccination was 25.2 years (10–64) years. No patient has reported a significant adverse event, including local site reactions or fever >38. Pre and post vaccine titers are currently available in 41 patients transplanted for acute leukemia (n=22), CML (n=4), MDS (n=5), NHL (n=4), Hodgkin’s disease (n=1), hemoglobinopathy (n=4), or Wiskott Aldrich syndrome (n=1). Stem cell donors were an HLA matched sibling (n=23) or unrelated donor (n=18). Fifty-nine percent of patients received T-cell-depleted allografts and the remaining 41% received unmodified allografts. Patients were vaccinated at a median of 4.5 years (range: 0.8–14 years) after transplantation. The majority of patients had no detectable pertussis titers prior to immunization. In an effort to provide early protection against pertussis, ten patients received Tdap as their primary tetanus vaccine. The remainder received Tdap as a booster following one (n=4), two (n=3) or 3 (n=24) age appropriate tetanus/diphtheria containing vaccines. Response to TT (seroconversion >0.15 IU/ml or >3 fold increase) was significantly better when Tdap was used as a booster vaccine compared with use as the initial tetanus vaccine (74% vs 20%, p=0.003). Response to TT and diphtheria toxoid was also significantly better in patients who received Tdap following a series of three tetanus/diphtheria containing vaccines, compared with one or two (p=0.03). In contrast, only 7 patients developed a >2 fold increase in antibody titer against PT. Of these 7 responders, 6 were <15 years of age and three received a series of pediatric DTaP following HCT and prior to receipt of Tdap. These data demonstrate that Tdap should not be given as the primary tetanus vaccine post alloHCT, but should be used as a booster vaccine as recommended for the general population. It also shows that responses to reduced dose pertussis in this patient population are poor. This may reflect the limited immunogenicity of this low dose of PT in adolescents and adults whose T and B cells are naïve to pertussis. Strategies to improve pertussis response in this vulnerable population, such as administration of >1 Tdap and/or donor immunization prior to stem cell harvest, should be explored.