Immunogenicity of recombinant hepatitis B vaccine (rHBV) in recipients of unrelated or related allogeneic hematopoietic cell (HC) transplants.

Current European and US guidelines for recombinant hepatitis B vaccine (rHBV) after hematopoietic-cell transplantation (HCT) vary. The European Group for Blood and Marrow Transplantation (EBMT) recommends rHBV starting 6 to 12 months after HCT. Immunization is optional in the Centers for Disease Control and Prevention (CDC) guidelines. Nevertheless, rHBV is required for re-entry to school and certain workplaces. To determine the immunogenicity of rHBV following HCT, the prevaccine and postvaccine titers of 292 allogeneic transplant recipients who were immunized with rHBV were analyzed. Immunization was initiated in patients off immunosuppression who achieved specific minimal milestones of immune competence. Overall, 64% of patients seroconverted. In multivariate analyses, response was adversely affected by age older than 18 years (P < .01) and history of prior chronic graft-versus-host disease (GVHD; P < .001) but not by donor type or by use of T-cell depletion, adoptive immunotherapy, or rituximab. By comparison, 89% of rHBV nonresponders mounted a 3-fold or greater rise in polio titers following 3 doses of inactivated poliovirus. These data demonstrate that the rate of seroconversion following rHBV is lower in allogeneic HC transplant recipients compared with age-matched healthy controls. The data emphasize the need to document prevaccine and postvaccine titers to ensure response and suggest that immunization guidelines based on time interval from HCT, irrespective of immune competence, may not ensure adequate protection against certain vaccine-preventable diseases.

TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation.

Toll-like receptors (TLRs) transmit signals in response to Aspergillus fumigatus conidia and hyphae. In this preliminary study, we examined the association between single nucleotide polymorphisms (SNPs) in TLR1, TLR4, and TLR6 genes and development of invasive aspergillosis (IA) in 127 allogeneic hematopoietic stem cell transplant recipients consisting of 22 patients with IA and 105 unaffected control subjects. The following SNPs and their pairwise interactions were considered in the model: TLR1 (239G > C, 743A > G, 914A > T, 1805G > T), TLR4 (896A > G, 1196C > T), and TLR6 (359T > C, 745C > T, 764C > T). No association was found between donor SNP and the risk of IA. Analysis of recipient SNP data showed that the presence of TLR1 239G > C (Arg80 > Thr) or the presence of both TLR1 743A > G (Asn248 > Ser) and TLR6 745C > T (Ser249 > Pro) is associated with IA (odds ratio = 1.30, 95% confidence interval = 1.13 to 1.50; P < .001). Further analyses using a prospective cohort may enable us to identify TLR polymorphisms associated with the susceptibility to IA within a defined interval among immunocompromised patients.

Prevention of peritransplantation viridans streptococcal bacteremia with early vancomycin administration: a single-center observational cohort study.

BACKGROUND: Viridans streptococcal bacteremia (VSB) after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with substantial mortality. Prevention of this serious complication is therefore a high priority. The objective of this study was to evaluate the effect of early vancomycin administration on rates and outcomes of VSB. METHODS: We analyzed the effect of early vancomycin on the incidence of VSB in a cohort of 430 consecutive HSCTs performed during the period of 1 January 1998 to 30 September 2002. The primary end point was time to diagnosis of VSB. Early vancomycin was defined as >or=2 doses of vancomycin between days -7 through +7 after HSCT or diagnosis of VSB, whichever occurred first. Risk factors for VSB were identified in univariate and multivariate Cox proportional hazard models. RESULTS: The incidence of VSB in the cohort was 7.4%. The incidence of VSB in patients who did not receive early vancomycin was 24.8%, compared with 0.3% in patients who did (P<.001). Additional risk factors were female sex, conditioning with total body irradiation, and diagnosis of chronic myelogenous leukemia. CONCLUSIONS: The attributable mortality rate for VSB in our cohort was 21%. Early vancomycin was associated with decreased VSB (hazard ratio, 0.02; 95% confidence interval, 0.003-0.19) after controlling for age, sex, underlying disease, and transplantation variables. The benefits of vancomycin prophylaxis for the prevention of VSB and associated mortality need to be evaluated in a prospective clinical trial.