Immunization for Bone Marrow Transplant Recipients

353 In a previous issue of the journal, we reviewed immunization in healthy, immunocompetent adults (1). In the present issue, we consider immunization in adults who have undergone bone marrow transplants. Bone marrow transplantation (BMT) has become a common procedure for the treatment of several types of hematological malignancies, aplastic anemia and several congenital deficiencies of the bone marrow and immune systems (2). By virtue of the pretransplant preparatory regimens, a temporary state of combined immunodeficiency occurs in all patients after transplantation, with functional recovery of humoral and cell mediated immunity potentially taking a year or longer to develop (2). Multiple components of the host protective mechanisms are impaired, including mucosal barriers, granulocytes, natural killer cells, T cells and B cells (3). Part of the immunodeficiency includes loss of the immune memory that has accumulated over many years of exposure to infectious agents and vaccines (4). While there are some data to support the transfer of memory B cells from donor to recipient, most B cells in BMT survivors have probably developed from bone marrow stem cells, which need to be stimulated to provide long term protection (3). The immunodeficient state is further modified by the use of immunosuppressive therapies, the occurrence of graft-versus-host disease (GVHD) and infection with cytomegalovirus. This immunodeficient state puts the hematopoietic stem cell recipient at increased risk for infection with a variety of pathogens, some of which are preventable by vaccine. An understanding of the level of immune responsiveness after BMT is important, not only for recognizing the risk for infection, but also for determining the optimal timing for vaccine delivery. POST-BMT IMMUNITY AGAINST VACCINE PREVENTABLE INFECTIONS Post-BMT antibody levels and in vitro cell mediated immune responsiveness to a variety of bacterial and viral pathogens have been studied in a number of patients, largely in the context of small, post-BMT vaccine studies. Most studies have determined that antibody levels fall after BMT and continue to fall over a number of years, despite reconstitution of the immune system. The roles of transplant source (allogeneic compared with autologous), GVHD (acute and chronic) and natural versus vaccine-induced immunity in the loss of antibody after BMT have not been completely elucidated. In the 1980s, Ljungman et al (5) found that 77% of 48 allogeneic BMT patients and 71% of their donors were seropositive for tetanus toxoid (TT) before BMT. One year after BMT, only half of the previously immune and none of the nonimmune patients had detectable antibodies. At two years, none of the nonvaccinated patients was seropositive (5). Of note was a positive correlation between the patients’ antibody levels before transplant and one year after transplant, raising the possibility of a role for immunization of patients before BMT to improve protection after BMT (5). The authors did not find that tetanus immunity was transferred to seronegative patients from their seropositive donors, but the study involved a small number of patients (5). This fall in antitetanus antibodies has been confirmed by other investigators in both allogeneic and autologous BMT patients (6-8), and one investigator also examined and found a positive correlation between pretransplant and post-transplant antibody levels (6). Immunization for bone marrow transplant recipients