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2024-05-15T13:22:11.000Z

Effects of antibiotic exposure following allo-HCT with non-myeloablative Flu-TBI conditioning

May 15, 2024
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Learning objective: After reading this article, learners will be able to cite a new clinical development in graft-versus-host disease.

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Antibiotics play a significant role in acute gastrointestinal graft-versus-host disease (GI-GvHD) following allogeneic hematopoietic cell transplantation (allo-HCT). Antibiotic use can negatively impact microbial diversity and exacerbate GI-GvHD, resulting in higher rates of non-relapse mortality and worse overall survival (OS) outcomes in patients.  

Most current data on the use of antibiotics in HCT are limited to the setting of reduced intensity conditioning and myeloablative HCT, with a lack of data from non-myeloablative (NMA) HCT. Understanding the effects of antibiotic exposure is important in the NMA HCT setting, where mucosal barrier integrity is less compromised compared with reduced intensity conditioning and myeloablative HCT, allowing for a focused analysis of the sole impact of antibiotic use on GI-GvHD and HCT outcomes. 

Van Groningen et al. recently published an article in Leukemia & Lymphoma on the impact of antibiotic exposure on GI-GvHD following allo-HCT with NMA conditioning. Here, we summarize their findings. 

Methods1

  • This was a single-center retrospective analysis that included patients who received allo-HCT following fludarabine/higher total body irradiation (Flu-TBI) -based NMA conditioning for a hematologic malignancy. 

  • Flu-TBI conditioning consisted of 30mg/m2 fludarabine on Days −4, −3, and −2, and low-dose TBI on Day −1. 

  • In the event of mismatched unrelated donor transplant, patients received additional in vivo T cell depletion with 2mg/kg/day rabbit-ATG on Days −8, −7, −6, and −5.  

  • Antibiotics received by patients included ciprofloxacin, ceftazidime, meropenem, ceftazidime, metronidazole, and valacyclovir. 

  • Key outcome measures included non-relapse mortality (NRM), relapse-free survival (RFS), OS, and GvHD relapse-free survival (GRFS). 

Key findings1

  • A total of 150 patients were included that had received Flu-TBI-based NMA conditioning. 

  • Median patient age was 59 years and 53% were male.  

  • Antibiotic exposure occurred in 60% of patients, with 40% receiving prophylactic ciprofloxacin, and 20% receiving broad-spectrum antibiotics.  

  • NRM at 1 year was 19% in patients who received antibiotics, and 10% in those who did not.  

  • OS and RFS were not significantly affected by antibiotic exposure. 

  • GRFS was significantly lower in patients receiving antibiotics vs those who did not (42% vs 55%). 

  • Antibiotic exposure was shown to play a significant role in the occurrence of GvHD (Figure 1). 

Figure 1. Incidence of acute and chronic GvHD by antibiotic exposure status*

GvHD, graft-versus-host disease; NS, not significant. 
*Data from Van Groningen, et al.1  

 

Key learnings 

  • These data show that antibiotic exposure was associated with GI-GvHD, NRM, and GRFS in patients receiving truly NMA HCT. 

  • In this setting, antibiotics can and should be utilized, restrictively. 

  • Additional studies will be needed to define microbial composition and alterations in patients receiving Flu-TBI-based HCT, confirming the above findings. 

  1. van Groningen LFJ, van Dorp S, Bremmers MEJ, et al. Significant impact of antibiotic exposure on GI-GVHD, NRM, and GRFS following allogeneic HCT with non-myeloablative Flu-TBI conditioning. Leuk Lymphoma. 2024. Published online ahead of print. DOI: 10.1080/10428194.2024.2331081 

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