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Background Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination reduces the risk and severity of coronavirus disease 2019 (COVID-19), several variables may impact the humoral response among patients undergoing hematopoietic stem cell transplantation (HSCT). Methods A retrospective chart review was conducted among SARS-CoV-2-vaccinated HSCT recipients between 2020 and 2022 at a single center in Boston, Massachusetts. Patients age ≥18 years who received doses of Pfizer, Moderna, or J&J vaccines were included. Anti-spike (S) immunoglobulin G (IgG) titer levels were measured using the Roche assay. Responders (≥0.8 U/mL) and nonresponders (<0.8 U/mL) were categorized and analyzed. Multivariable linear and logistic regression were used to estimate the correlation coefficient and odds ratio of response magnitude and status. Results Of 152 HSCT recipients, 141 (92.8%) were responders, with a median (interquartile range [IQR]) anti-S IgG titer of 2500 (107.9–2500) U/mL at a median (IQR) of 80.5 (36–153.5) days from last dose, regardless of the number of doses received. Higher quantitative titers were associated with receipt of more vaccine doses (coeff, 205.79; 95% CI, 30.10 to 381.47; P =.022), being female (coeff, 343.5; 95% CI, −682.6 to −4.4; P =.047), being younger (<65 years; coeff, 365.2; 95% CI, −711.3 to 19.1; P =.039), and not being on anti-CD20 therapy (coeff, −1163.7; 95% CI, −1717.7 to −609.7; P =.001). Being male (odds ratio [OR], 0.11; 95% CI, 0.01 to 0.93; P =.04) and being on anti-CD20 therapy (OR, 0.16; 95% CI, 0.03 to 0.70; P =.016) were associated with nonresponse. Conclusions Overall, most HSCT recipients had high SARS-CoV-2 antibody responses. More vaccine doses improved the magnitude of immune responses. Anti-S IgG monitoring may be useful for identifying attenuated vaccine-induced responses. [ABSTRACT FROM AUTHOR]