Low incidence of invasive aspergillosis in allogeneic stem cell transplant recipients receiving amphotericin B inhalation prophylaxis

Abstract

In this retrospective study we evaluated the impact of amphotericin B (AmB) deoxycholate inhalation prophylaxis on invasive aspergillosis (IA) in 611 allogeneic stem cell transplant (alloSCT) recipients and their tolerance of the inhalations. The inhalations were not used in 1996-2000 (Period I). In 2001-2005 (Period II) all patients with acute graft-versus-host disease treated with high-dose methylprednisolone used the inhalation prophylaxis with a dose of 25 mg daily. No systemic antifungal prophylaxis was routinely used during the study period. IA was detected in 17 (13 proven, 4 probable) out of 257 (6.6%) patients transplanted in Period I and in 9 (6 proven, 3 probable) out of 354 (2.5%) patients transplanted in Period II (P=0.007). The median time to the diagnosis of IA was 95 days and 155 days post transplant in the 2 periods (P=0.225). The mortality of the patients with IA was 94.1% and 66.6% in Period I and Period II. The median duration of AmB inhalation prophylaxis was 84 days. Breakthrough IA was detected in 1 of the 111 (1%) patients during the prophylaxis. No discontinuation of prophylaxis due to side effects was recorded. Overall, with a median follow-up of 3.5 and 4.6 years, 42.4% and 59% of the patients were alive in Period I and Period II, respectively (P=0.001). In conclusion, the incidence of IA fell during the AmB inhalation prophylaxis, and the inhalations were well tolerated. Mortality of patients with IA was high. The overall survival of patients was significantly higher in Period II, indicating the advances made in SCT therapy over the 10-year period.

Primary Prophylaxis of Invasive Fungal Diseases in Allogeneic Stem Cell Transplantation: Revised Recommendations from a Consensus Process by Gruppo Italiano Trapianto Midollo Osseo (GITMO)

“…Since the GITMO Consensus Conference published in 2009, only few studies on PAP in the allo-HSCT population have been published [42][43][44][45][46][47][48][49][50][51], and only 2 of them were prospective, randomized, multicenter trials [43,46] (Table 3).…”

“…There was no difference in incidence of proven/probable IFD (1.3% versus 2.1%) or survival to day 180 (81.9% versus 80.9%) for voriconazole and itraconazole, respectively. Nihtinen, 2012 [47] Retrospective, single center in patients with acute GVHD. AmB deoxycholate inhalation for a median duration of 84 days (n¼ 354) versus historical control (n ¼ 257).…”

Comparison of long‐term and short‐term administration of itraconazole for primary antifungal prophylaxis in recipients of allogeneic hematopoietic stem cell transplantation: a multicenter, randomized, open‐label trial

“…The benefits of antifungal prophylaxis should outweigh the drug toxicities . A growing body of clinical evidence suggests that antifungal prophylaxis reduces fungal infection‐related mortality and transplant‐related mortality in patients undergoing HSCT, thus improving survival .…”

Foiling fungal disease post hematopoietic cell transplant: review of prophylactic strategies

“…Several trials have examined the use of amphotericin B for prophylaxis of IFD. [48][49][50][51][52][53] Smaller studies have demonstrated that amphotericin is safe and effective in preventing IFD in HCT patients. 48,49 However, trials comparing amphotericin to posaconazole have demonstrated higher rates of adverse effects with amphotericin, such as nephrotoxicity.…”

“…50,53 Retrospective trials using aerosolized amphotericin B have shown this to be a safe and effective strategy for fungal prophylaxis in HCT, but there are no published prospective trials examining its efficacy. 51,52 Voriconazole has been studied extensively as a prophylactic agent in the HCT setting. 33,[54][55][56][57][58] Adverse effects of voriconazole include hepatotoxicity, prolongation of the QTc interval and visual disturbances.…”