Real-World Efficacy of Anti-Fungal Prophylaxis in Patients Treated for Acute Gastrointestinal Graft-Versus-host Disease (GI-GVHD)

Aim

Allogeneic progenitor cell transplant (HPCT) recipients who develop acute gastrointestinal graft-versus-host disease (GI-GVHD) are at increased risk of developing invasive fungal infections (IFI). Randomised control trial data supports the use of mould-active fungal prophylaxis in HPCT patients with grade II-IV GVHD (Ullman et al. 2007). We aimed to assess our unit's use of anti-fungal prophylaxis and describe the incidence and species of breakthrough IFI in patients with GI-GVHD.

Method

We conducted a retrospective audit of patients who underwent HPCT at our institution between 2011-2016 and identified those who were treated for acute GI-GVHD using a minimum of prednisone 1mg/kg or equivalent. For those patients the following details were collected: presence of any prior IFIs, anti-fungal prophylaxis before and after initiation of steroids, and the incidence of new IFIs within 6 months of commencing steroids.

Result

Of the 551 HPCT performed during this period, 74 evaluable patients were treated for GI-GVHD. All patients received anti-fungal prophylaxis prior to steroid commencement (66.2% received fluconazole, 10.8% posaconazole, 20.2% voriconazole and 2.7% other). Post steroids 35.1% remained on fluconazole, 21.6% received posaconazole, 35.1% received voriconazole, and 8.1% received other anti-fungals. Of the 26 patients remaining on fluconazole, 9 were transitioned to mould-active prophylaxis at a later time.

Twelve patients (16.2%) experienced a breakthrough IFI (6 definite and 6 probable). In the 42 patients receiving posaconazole or voriconazole, 7 (16.7%) experienced breakthrough IFI, compared with 3 (11.5%) in the fluconazole cohort. Two other cases occurred in patients who received caspofungin. Notably, patients receiving mould-active fungal prophylaxis developed mucormycosis, Fusarium and Scedosporium infections whereas fluconazole lead to invasive aspergillosis.

Conclusion

Despite anti-fungal prophylaxis, real-world GI-GVHD patients remain at particularly increased risk of developing IFI. Anti-mould prophylaxis is associated with lower incidence of invasive aspergillosis but higher incidence of non-Aspergillus mould. Further studies investigating optimal anti-mould strategies are warranted.