Patterns and Correlates of Immunity to Vaccines in Children Following Allogeneic Hematopoietic Stem Cell Transplantation

Background: Limited data is available on vaccine immunity status following allogeneic hematopoietic stem cell transplantation (HSCT) in children. We investigated vaccine titers along with other immunologic parameters and sought correlations with the patient characteristics in this study. Methods: Twenty-eight children (1-20 years) with available vaccine titers following allogeneic HSCT (performed between 2009 and 2016) prior to starting re-immunization were included in this retrospective analysis. Antibody concentrations against hepatitis A and B, poliovirus serotypes 1, 2 and 3, tetanus, diphtheria, measles, mumps, rubella, varicella, and 14 pneumococcus serotypes were measured as our planned monitoring. Chi-Square test and univariate analysis of variance were used for statistical evaluation. Results: Median age was 6.5 years (1-20), 15 (54%) were males and 15 (54%) had non-malignant diseases. Bone marrow was the stem cell source in 23 (82%). Eighteen patients (64%) received myeloablative, 6 (21%) non-myeloablative, and 5 (15%) reduced intensity conditioning. Median time to re-vaccination from HSCT was 13.5 months (7-38). All patients had normal serum IgG levels. Protective antibody levels were found for hepatitis A in 79% of the patients, hepatitis B in 46%, all poliovirus serotypes in 50%, tetanus in 50%, diphtheria in 29%, measles in 54%, mumps in 43%, rubella in 50%, varicella in 46%, and 3 7/14 pneumococcus serotypes in 54%. Pneumococcal serotypes 4 and 12F (25%) have the lowest and 5 and 19F highest (96%) immunity rate. In univariate analysis, patients with non-malignant diseases (P = .03) and no history of GVHD (P = .04) had more protective titers. However, type of conditioning regimen, ATG use, stem cell source, gender, age at diagnosis, time to HSCT from diagnosis, donor age, time to engraftment, time to re-vaccination from HSCT, CD4+, CD8+, NK, and B cells at re-vaccination did not have impact on the vaccine immunity status overall. A significant positive correlation was found in titers against the microorganisms or serotypes of the same microorganism whose vaccines administered together, including correlation between polio serotype 1 and 2 (P = .021), polio serotype 2 and 3 (P = .004), diphtheria and tetanus (P = .001), mumps and measles (P = .008), and rubella (P = .004), and between the majority of pneumococcus serotypes. Conclusion: Vaccine immunity was variable with the lowest rate for diphtheria and highest for hepatitis A at the time of re-vaccination following allogeneic HSCT. Recipients with non-malignant diseases have higher degrees of sero-positivity that may be associated with lack of prior chemotherapy and/or history of frequent transfusions.