Patients who have undergone autogolous peripheral blood stem cell transplantation (APBSCT) have a prolonged functional immunodeficiency that precludes active immunization in the early posttransplant period. Since it was previously found that the absolute number of mature dendritic cells (DC) in the peripheral blood was lower than normal early after APBSCT, we hypothesized that agents stimulating DC number or function would provide adjuvant activity for active immunization. Studies in animal models suggested that sargramostim (GM-CSF), a cytokine that stimulates maturation and function of DC, would be an effective adjuvant for immunization using peptide or protein antigen. In this study, we tested the effect of GM-CSF as an adjuvant for immunization after APBSCT. Patients with breast cancer in remission 4-6 weeks after APBSCT were eligible if they had hematopoietic recovery, were not using hematopoietic growth factors, were not to receive radiation or cytotoxic agents within 6 weeks of study entry, and had no nonresolved organ toxicity. There were 10 évaluable patients were immunized with tetanus toxoid im alone at a median of 34 days after APBSCT, and 10 immunized with tetanus toxoid im and GMCSF 250 ug sc at a median of 28 days after APBSCT. Follow-up studies included peripheral blood lymphocyte subset quantitation, lymphocyte proliferative response to tetanus toxoid, serum antibody titers, and tetanus toxoid skin tests. One patient had an exuberant response to the initial tetanus toxoid immunization and was not skin tested. Of the patients receiving tetanus toxoid alone, when tested at a median of 66 days after APBSCT, all had an increase in the absolute numbers of B cells, 1/9 had a significant increase in antibody titer, and 5/10 had a cell-mediated response. For those receiving tetanus toxoid and GM-CSF, when tested at a median of 77 days after APBSCT, all had an increase in the absolute numbers of B cells, 1/9 had a significant increase in antibody titer, and 5/7 had a cell-mediated response. There was no correlation between the absolute lymphocyte subset counts and development of an antibody or cell-mediated response to tetanus with or without GM-CSF. We conclude that GM-CSF may increase the cell-mediated response to tetanus toxoid immunization early after APBSCT, but the antibody response remains poor.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology