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 to autologous), GVHD(acute and chronic), and natural versus vaccine-induced immunity in the loss of antibody after BMT have not been completely elucidated.

In view of the studies demonstrating loss of protective antibodies in patients who have undergone BMT, a number of investigators have examined responses to immunization in this group of patients. Most studies were nonrandomized, included small numbers of patients and utilized different immunization schedules. It is, therefore, difficult to make comparisons between different regimens and patient groups. Furthermore, due to the rarity of most of these infections in adults, outcomes in terms of occurrence of infection have not been evaluable. However, with the exception of pneumococcal immunization, responses to vaccines after BMT are generally good. Receiving more than one vaccine dose has been consistently associated with a better antibody response, in support of the theory that B cell immunity derives largely from donor marrow stem cells rather than memory cells (5,10-12,16-19). There is little evidence to support one dosing schedule over another (6,7,12,13,16,17). For tetanus and polio vaccines, there have been no differences noted between those with and without GVHD in terms of response rate (5,6), although those without GVHD tend to have higher antibody levels (6,12). Likewise, there is no apparent difference between autologous and allogeneic BMT recipients in response to vaccine (19) and between those who receive peripheral blood stem cells rather than bone marrow (20). On the other hand, acute and chronic GVHD did have an impact on response to pneumococcal polysaccharide vaccine, a poor immunogen (13), as did early vaccination after transplantation and corticosteroid therapy (21). Although involving small numbers of patients, none of the studies reported serious adverse events associated with immunization and most did not even comment on frequency of minor reactions (Table 1).

The recent update of the Canadian Immunization Guidelines (27) has a section dealing with immunization in immunocompromized patients, including BMT patients. The authors acknowledge that while there is a good theoretical basis for providing immunization, there are no conclusive data to support the best schedule, the need for boosters, efficacy in disease reduction or cost benefit. Diphtheria and TT, inactivated poliovirus, Hib, influenza and pneumococcal vaccines are recommended routinely after BMT (27). No specific dosing schedules are given. Meningococcal and hepatitis A vaccines are recommended if indicated, hepatitis B vaccine as per routine use, while MMR, varicella and yellow fever vaccines may be considered at 24 months if there is no immunosuppressive therapy or disease (27). Oral polio, typhoid and cholera vaccines, as well as Bacille Calmette-Guerin are contraindicated (27). The United States Eastern Oncology Cooperative Group indicated in 1994 that it is probably reasonable to consider a number of vaccines at the end of one year without making any clear recommendations (2). In their 2000 guidelines for hematopoietic stem cell transplant recipients (Table 2), the United States Centers for Disease Control and Prevention (CDC) recommended a number of vaccines and offered immunization schedules (4). The CDC and Canadian guidelines are similar except that the CDC recommends that varicella-zoster vaccine use, even in those presumed to be immunocompetent, be restricted to the research setting until further information is available (4). The European Group for Blood and Marrow Transplantation recommends in its updated guidelines that all BMT patients receive TT, diphtheria toxoid, inactivated poliovirus, pneumococcal, H influenzae and influenza vaccines (28). Measles and rubella immunization is considered an individual recommendation based on risk/benefit assessment with vaccination not to be given before 24 months in the allogeneic recipient (28).