A Third Dose COVID-19 Vaccination in Allogeneic Hematopoietic Stem Cell Transplantation Patients (preprint)

We previously reported that a second dose of COVID-19 mRNA vaccine was safe and effective for allogeneic hematopoietic stem cell transplantation (HSCT) patients. However, some of these patients did not achieve seroconversion. Here, we investigated the safety and efficacy of a third dose of COVID-19 mRNA vaccine in Japanese allogeneic HSCT patients. Antibody titers against the S1 spike protein were measured using the QuaResearch COVID-19 Human IgM IgG ELISA kit. The previous study included 25 allogeneic HSCT patients who received two doses of COVID-19 mRNA vaccine. Following the exclusion of three patients because of the development of COVID-19 (n = 2) and loss to follow-up (n = 1), the study evaluated 22 allogeneic HSCT patients who received a third dose of COVID19 mRNA vaccine (BNT162b2 [n = 15] and mRNA1273 [n = 7]). Median age at the time of the first vaccination was 56 (range, 23-71) years. Median time from HSCT to the third vaccination and from the second to the third vaccination was 1842 (range, 378-4279) days and 219 (range, 194-258) days, respectively. Five patients were receiving immunosuppressants at the third vaccination, namely calcineurin inhibitors (CI) alone (n = 1), steroids alone (n = 2), or CI combined with steroids (n = 2). Median optical density of S1 IgG titers before and after the third dose was 0.099 (range, 0.001-0.713) and 1.315 (range, 0.006-1.730), respectively. Among 22 evaluable patients, 21 (95%) seroconverted after the third dose. Four of the five patients treated with steroids or CI seroconverted after the third vaccination. One patient with a serum IgG level of 173 mg/dL who received steroids did not achieve seroconversion. On one-week follow-up, none of our patients had > grade 3 or serious adverse events, new onset graft versus host disease (GVHD), or GVHD exacerbation after vaccination. The most frequent adverse event was mild pain at the injection site. A third dose of the BNT162b2 and mRNA-1273 COVID-19 vaccines was safe and effective for allogeneic HSCT patients.

Safety and immunogenicity of BNT162b2 mRNA COVID-19 vaccine in Japanese patients after allogeneic stem cell transplantation. (preprint)

Patients who have undergone hematopoietic stem cell transplantation (HSCT) for hematological disease experience high mortality when infected by coronavirus disease 2019 (COVID-19). However, the safety and efficacy of COVID-19 vaccine in HSCT patients remains to be investigated. We prospectively evaluated the safety and immunogenicity of BNT162b2 mRNA COVID-19 vaccine (Pfizer BioNTech) in 25 Japanese allogeneic HSCT patients in comparison with 19 healthy volunteers. While anti-S1 antibody titers in almost all healthy volunteers after the second dose were higher than the cut-off value reported previously, levels in HSCT patients after the second dose were diverse. Nineteen patients (76%) got seroconversion of anti-S1 IgG. Median optical density of antibody levels in HSCT patients with low IgG levels (< 600 mg/dL), steroid treatment, or low lymphocytes (< 1000 /L) was significantly lower than that in the other HSCT patients. There were no serious adverse events (> Grade 3), no new development or exacerbation of graft-versus-host disease after vaccination. We concluded BNT162b2 mRNA vaccine is safe and effective in Japanese allogeneic HSCT patients.