Incidence of Engraftment Syndrome with and without Budesonide Prophylaxis in Patient with Multiple Myeloma Undergoing Autologous Stem Cell Transplant

Engraftment syndrome (ES), a rare post-transplant complication, has been defined differently across the existing literature. This study aims to determine if budesonide prophylaxis reduces the incidence of ES after autologous hematopoietic cell (auto-HCT) for patients with multiple myeloma (MM), as defined by three separate published criteria - Spitzer1, Maiolino2, and Dhakal3, respectively.

A single-center, IRB-approved, retrospective review was conducted on adult patients who received auto-HCT for the treatment of MM between January 2017-October 2023. Based on results of the Dhakal study reporting the benefit of budesonide to prevent ES, our local institution made a practice change in October 2021 to prescribe budesonide 3mg by mouth three times a day, beginning on day +5 until discharge, for ES prophylaxis in all patients with a diagnosis of MM undergoing auto-HCT. Patients were divided into those who did not receive budesonide prophylaxis (n=169) and those who did receive budesonide prophylaxis (n=144). Primary endpoint was incidence of ES by each criteria. Secondary endpoints included receipt of steroids to treat ES, time to engraftment, and 30- and 100-day mortality rates. Exploratory endpoints were new start antibiotics in the peri-engraftment period and number of doses of anti-diarrheal and anti-emetic agents.

Overall, most patients were Caucasian or African-American, male, and the median age was 66 years. No difference existed between groups for any demographic factor including dose of melphalan, receipt of plerixafor, or median number of CD34 cells infused (all p>0.05). No difference existed between the two groups with respect to the primary outcome of incidence of ES by Spitzer, Maiolino, or Dhakal criteria or by provider documented ES (all p>0.05). Further, no difference existed between the groups with respect to the secondary or exploratory outcomes (all p>0.05); however, those who received budesonide were less likely to receive new treatment with an antibiotics within 3 days before or 10 days after neutrophil engraftment (20.9% vs 47.5%, p<0.001).

Our findings show budesonide does not appear to reduce the incidence of ES when utilizing Spitzer or Mailoino criteria. The low overall rates of ES by Spitzer, Mailoloino, and provider documentation in this study suggest a preventative strategy may not be warranted. However, reduction in incidence of new onset febrile neutropenia in the peri-engraftment period warrants further study.

Kota:Novartis: Honoraria; Kite Pharma: Honoraria; Pfizer: Honoraria.

This study aims to determine if budesonide prophylaxis reduces the incidence of ES after auto-HCT. Budesonide is indicated in the treatment of Crohn's disease to reduce gastrointestinal inflammation.