PURPOSE: Engraftment syndrome (ES), a rare post-transplant complication, has been defined differently across the literature. This study aims to determine if budesonide prophylaxis reduces ES after autologous hematopoietic cell transplantation (auto-HCT) for patients with multiple myeloma (MM), as defined by the published Spitzer or Maiolino criteria or by the ES definition used by Dhakal et al. METHODS: A single-center retrospective review was conducted on adult patients who received auto-HCT for MM between January 2017 and October 2023. Patients were divided into those who did not receive budesonide prophylaxis (n = 169) versus those who did (n = 144). The primary endpoint was an incidence of ES by the definition used by Spitzer, Maiolino, and Dhakal et al., respectively. Secondary endpoints included receipt of steroids to treat ES, hospital length of stay, engraftment, and 30- and 100-day mortality rates. Exploratory endpoints were antibiotics started in the peri-engraftment period and number of anti-diarrheal and anti-emetic doses. RESULTS: No difference existed between groups in the primary outcome by the ES definition used by Spitzer, Maiolino, or Dhakal et al. (all p >
0.05). Further, no difference existed with respect to any secondary outcomes (all p >
0.05) except a lower incidence of receipt of antibiotics in the peri-engraftment period for those who received budesonide. CONCLUSION: Our findings suggest concordance between Spitzer and Maiolino criteria with clinically documented ES, with higher incidences when the ES definition used by Dhakal et al. is utilized. Larger controlled trials need to be performed to validate these findings.