Immunogenicity and Safety of Booster SARS-CoV-2 mRNA Vaccine Dose in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients are susceptible to severe outcomes of Coronavirus disease 2019 (COVID-19). Most guidelines recommend a fourth dose (ie, booster) of COVID-19 vaccine to reduce the infection risk, and observational studies are needed to determine the immunogenicity and safety of the booster dose in this population. The primary outcome was to determine the quantitative anti-receptor-binding domain (RBD) antibody titers after the fourth dose of the COVID-19 vaccine. The secondary outcomes included adverse effects and all-cause mortality. This single-group prospective cohort included allogeneic HSCT recipients age ≥18 years who received their fourth dose of COVID-19 mRNA vaccine between December 15, 2021, and August 2, 2022. We excluded patients with a history of COVID-19 diagnosis and those who received i.v. Ig within 21 days of antibody testing or rituximab within 6 months before study entry. We used regression models to determine the contributing factors significantly associated with post-fourth dose anti-RBD titer. Sixty-seven patients (median age, 59.5 years; IQR, 53.5 to 65.5 years; 33 males [61%]) received the fourth dose of vaccine, and 54 were included in the anti-RBD titer analysis. The median anti-RBD titers at 4 to 6 weeks after the third and fourth doses differed significantly (13,350 U/mL [IQR, 2618 to 34,740 U/mL] and 44,500 U/mL [IQR, 11,163 to 84,330 U/mL], respectively; P < .0001). In univariate analysis, the post-third dose anti-RBD titer (β = .70; 95% CI, .54 to .87; P < .001) and treatment with mycophenolate compounds (β = -1.05; 95% CI, -1.97 to -1.12; P = .03) significantly predicted the antibody response to the fourth dose. In multivariate analysis, the inverse association between treatment with mycophenolate compounds and the post-fourth dose anti-RBD antibody titer was not significant (β = -.57; 95% CI, -1.32 to .19; P = .14), whereas the significant association between the anti-RBD titers following the third and fourth doses did not change considerably (β = .66; 95% CI, .47 to .86; P < .001). The most frequent adverse event was vaccination site soreness (44%), followed by fatigue (16%), myalgia (4%), and headache (2%). No recipient experienced new or worsened preexisting graft-versus-host disease within 40 days of vaccination, and no patient died. Six patients (11%) developed breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection not associated with hospitalization or severe outcomes. The fourth dose of the COVID-19 vaccine appears to be highly immunogenic and safe in allogeneic HSCT recipients. Further studies are needed to determine the neutralizing antibody titers against SARS-CoV-2 subvariants and the effectiveness and immunogenicity of bivalent vaccines in allogeneic HSCT recipients.