B-cell immunity in patients with hematological malignancies and after stem cell transplantation : studies with special reference to tetanus and pneumococcal immunity

Treatment of malignancies with cytotoxic chemotherapy and/or bone marrow or stem cell transplantation also suppress the immune system which becomes incapable of controlling infections. Therefore infections can remain a serious problem for an extended period in these patients. The aims of these studies was to assess the immunological status against tetanus and pneumococci and the need of revaccinations. It was hypothesized that the immunity of the donor replaces the immunity of the patient after allogeneic bone marrow transplantation (BMT).

However, recipients of allogeneic marrow grafts frequently lost pretransplant immunity against tetanus after transplantation. After reimmunization with tetanus toxoid all patients responded with an adequate antibody production. Our further studies have shown similar findings in recipients of autologous grafts; the tetanus. immunity was defective both after autologous bone marrow transplantation (ABMT) and autologous peripheral stem cell transplantation (APBSCT). None of the patients who were seronegative seroconverted spontaneously without vaccination. Also patients treated for hematological malignancies with cytotoxic chemotherapy were in a high frequency unprotected against tetanus. The risk factors for loss of immunity against tetanus were increasing age, lymphoid malignancy and advanced disease stage. All these patient groups can therefore benefit from tetanus vaccination; a three dose immunization schedule was superior to obtain a long-lasting immunity.

Serologic studies of pneumococcal immunity showed that ABMT recipients retained pretransplant immunity, while it was lost in BMT patients. Immunization with pneumococcal polysaccharide vaccine was effective in BMT patients without chronic graft-versus-host disease (GVHD), while patients with chronic GVHD responded with an immature antibody pattern or did not respond at all. The poor antigenicity of the polysaccharide based vaccines was noted previously in immunocompromised patients. Therefore vaccines with polysaccharide conjugated to peptide were developed. The pneumococcal conjugate vaccine seems to elicit better immune response than polysaccharide vaccine in BMT patients with chronic GVHD.

The immune system matures slowly after transplantation and the patients have usually normalized levels of immunoglobulins within one year. The specific immunity is defective in immunocompromised patients and there is no correlation between levels of specific antibodies and total immunoglobulin levels.