Delayed ABLC prophylaxis after allogeneic stem‐cell transplantation

Abstract

Invasive fungal infections (IFI) are frequent causes of mortality after allogeneic stem-cell transplantation (SCT). A very important risk factor for IFI is the use of steroids. We used a risk-based chemoprevention in an open-labelled pilot study. All patients received oral fluconazole or itraconazole (200-400 mg day(-1)) during their neutropenic episode. Starting on day +30, patients receiving prednisone > or =30 mg day(-1) were switched to twice weekly Amphotericin-B-lipid-complex (ABLC) in a dose of 4 mg kg(-1). Patients receiving lower steroid doses continued on the fluconazole/itraconazole prophylaxis. Between 1999 and 2002, 100 patients were enrolled and followed for IFI for 1 year. Seven patients were started on therapeutic daily ABLC treatment before day +30 because of documented or suspected IFI; four had definite or probable aspergillosis, and two had candidaemia. Thirty patients did not need prophylactic ABLC; only one developed candidaemia. Sixty-three patients received ABLC prophylaxis for a median of 52 days (range: 1-289). Seven of these patients developed IFI; one definite and two probable cases of aspergillosis, one case of probable Trichosporon beigelii infection, and three cases of candidaemia. The twice weekly ABLC was well tolerated. This risk-based chemoprevention appears to be effective and might diminish the role of steroids as risk factor for IFI after allogeneic SCT. The relatively high incidence of early IFI suggests that additional prophylaxis for IFI may be indicated for poor-risk patients prior to day +30.

Comparison of Posaconazole Versus Weekly Amphotericin B Lipid Complex for the Prevention of Invasive Fungal Infections in Hematopoietic Stem-Cell Transplantation

“…Several studies have shown that a single weekly high dose of lipid formulation of amphotericin B (liposomal amphotericin B) used at a dose between 7.5 mg/kg and 15.0 mg/kg was effective. Twice weekly intravenous administration of ABLC seems to be well tolerated and effective in allo-HSCT recipients treated with corticosteroids who are at high risk of IFI (20). In a recent retrospective study, highdose liposomal amphotericin B once weekly seemed effective and well tolerated for prophylaxis of IFI after GVHD in allo-HSCT recipients (37).…”

“…However, there are no sufficient data to support the use of posaconazole as prophylaxis during the initial phase after allogeneic HSCT (allo-HSCT) (18,19). ABLC, on the other hand, is an antifungal agent with broad-spectrum activity and has also been used prophylactically (20,21). Because of its intravenous formulation, ABLC could be used for antifungal prophylaxis, particularly in patients who are unable to tolerate oral medications.…”

Minimizing the risk of recurrent or progressive invasive mold infections during stem cell transplantation or further intensive chemotherapy

“…Amphotericin B lipid complex (ABLC) has been used as primary prophylaxis beyond day 30 post allograft in a cohort of patients receiving ≥30 mg prednisolone/day (55). A twice‐weekly schedule of 4 mg/kg intravenously (IV) was well tolerated, and although breakthrough fungal infection (proven and probable aspergillosis and yeast infections) occurred in 7/63 patients (11%) treated for a median of 52 days, this was considered to be effective in this high‐risk population.…”