Vaccine responses after chemotherapy or stem cell transplantation in patients with hematological malignancies

Abstract

The prevention of infections in patients with hematological malignancies is important given the inherent immune deficiency associated with these diseases and the immunosuppressive effects of treatment. This thesis investigated the efficacy of vaccines against various pathogens among patients with hematological disease receiving chemotherapy or stem cell transplantation, including the longevity of vaccine responses. Paper I examines serum antibody levels against tetanus, diphtheria, and polio after standard chemotherapy in 104 patients treated for lymphoma or acute leukemia at median 18 months after completing treatment. Antibody levels were analyzed by enzyme-linked immunosorbent assay or neutralization tests and were compared with levels in age- and sex-matched healthy controls (n=47) and pretreatment levels (n=73). For tetanus, the number of seronegative patients increased during treatment (24 vs. 12 %) and antibody levels were reduced. A similar trend was observed for antibody levels against diphtheria. Immunity against poliovirus of serotypes 1 and 3 was preserved. Paper II describes a clinical vaccine trial that assessed the humoral response to four doses of vaccine against tick-borne encephalitis (TBE). A TBE vaccine (FSME-IMMUN®) was given starting nine months post-transplant to autologous (n=53) and allogeneic (n=51) stem cell transplant recipients. Serum samples were obtained prior to each vaccine dose (at nine, 10, 12, and 21 months) and three months after the last dose. Seventy-seven percent of patients after allogeneic stem cell transplantation (allo-HCT) and 80% after autologous stem cell transplantation (auto-HCT) achieved seropositivity following the last vaccine dose, compared with 100% among healthy controls. Graft-versus-host disease and ongoing immunosuppression were associated with poor vaccine responses. Paper III examines SARS-CoV-2 serum antibodies and T cell responses ex vivo before and after the third dose of an mRNA vaccine among 40 allo-HCT recipients. Many patients responded well, with antibodies above the upper detection limit. However, 16% were seronegative following vaccination and 49% of patients showed no T-cell reactivity against SARS-CoV-2 peptides. Paper IV analyzes serum antibody levels against tetanus and diphtheria among 143 long-term survivors after allo-HCT who had been vaccinated according to standard protocol with three doses of diphtheria and tetanus vaccine. Diphtheria immunity was poor and 40% of patients were seronegative. However, all patients had detectable antibodies against tetanus. To conclude, diphtheria immunity is poor in adult patients receiving chemotherapy as well as in long-term survivors after allo-HCT, and boosters may be considered. Vaccination against TBE is immunogenic when starting nine months after allo- or auto-HCT. The third dose of mRNA vaccine against COVID-19 elicits antibody responses in a majority of allo-transplanted patients. However, T cell responses remain poor in a significant proportion of these patients.