Immunogenicity of the Live Attenuated Varicella Vaccine Following Allogeneneic HCT.

Abstract 1137

Poster Board I-159

The live attenuated varicella vaccine (VARIVAX, Merck & Co., Inc) was licensed in 1995. Initial Advisory Committee on Immunization Practices [ACIP] recommended one dose of vaccine in children aged 12-18 months, catch-up vaccination of VZ seronegative children 19 months-12 years old, and vaccination of VZ seronegative older children and adults with close contact to persons at high risk for serious complications secondary to varicella. In 2006, due to breakthrough cases of varicella in recipients of a single dose of Varivax, the ACIP recommended 2 doses of vaccine in healthy children at 12-15 months and 4-6 years of age, a second dose in children, adolescents, and adults who previously received only one dose, and routine vaccination of all healthy persons 13 years or older without evidence of immunity. The ACIP also recommended Varivax in HIV-infected children and adults with circulating CD4+ T lymphocyte counts ≥ 200 cells/ul. There are no studies assessing Varivax following alloHCT. Nevertheless, up to 30% of children are VZ seronegative before transplant and many lose seroprotection following HCT. Due to the increased morbidity of primary varicella acquired later in life and the safety of Varivax in pediatric patients with ALL in remission on maintenance therapy, HIV infected children, and pediatric solid organ transplant recipients despite concomitant immunosuppression, this institution has instituted vaccination of VZ seronegative children following alloHCT. To reduce the potential risk of vaccination with a live attenuated vaccine, susceptible (VZ seronegative) patients had to be ≥ 2 years post HCT, off all immunosuppressive therapy, and similar to the ACIP recommendations in HIV-infected individuals have a circulating CD4 cell count >200 cells/ul. In addition, patients were required to have a PHA T cell proliferative response >75% of the lower limit of normal and demonstrate antibody response to >1 vaccine administered post HCT. To date, 34 patients have received Varivax following an HLA matched related (n=16), HLA mis-matched related (n=5) or unrelated (n=13) HCT. Patients were transplanted for acute leukemia (n=15), an immunodeficiency disorder (n=10), MDS/aplastic anemia (n=2), JMML (n=1), HLH (n=2), hemoglobinopathy (n=3), or Kostman's syndrome (n=1). Eleven of 34 patients received a T cell depleted graft. The median time to vaccination post HCT, age at HCT and age at vaccination were 4, 4, and 8.4 years, respectively. No patient had a serious adverse event. One of 34 patients developed a transient rash which resolved within 24 hours. Pre and post vaccine titers are currently available in 31 patients, 22 of whom responded (seroconverted) following Varivax. Four patients who failed to seroconvert were tested for development of T cell specific VZ response; three of the four responded. There was no significant difference in response between recipients of an unrelated or HLA matched related HCT. All 5 recipients of a TCD MM related HCT responded. These data suggest that Varivax is safe and immunogenic following HCT when given according to preset clinical and immunologic requirements.