Safety of a Weekly Administration of 7.5 mg/kg of Liposomal Amphotericin B (LAB) for Antifungal Prophylaxis in Patients Receiving High Dose Corticosteroids (CS) for Acute GVHD after Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT).

Background. RIC regimens are increasingly used for allo-SCT in elderly or patients not eligible for standard myeloablative allo-SCT. Such regimens have yielded promising results in terms of decreasing early transplant-related toxicities. However, acute GVHD remains a matter of concern in this setting. Of note, the use of high dose CS for GVHD treatment increases the risk of severe fungal infections in this high risk population usually presenting several comorbidities. Therefore, prophylactic strategies aiming to reduce this risk are needed.

Patient and Methods. We conducted a pilot single centre study in 15 adult patients receiving high dose CS (2 mg/Kg/day) for acute GVHD therapy after RIC allo-SCT. Treatment consisted of a 2 hour weekly infusion of 7.5 mg/kg LAB with a maximum of 8 total doses. The primary endpoint was the incidence of serious adverse events occurring during the course of prophylaxis treatment. Of note, safety was monitored with particular attention to nephrotoxicity in this relatively elderly population receiving concomitant nephrotoxic drugs such as cyclosporin A.

Results. Median age of these 15 patients with various hematological and non-hematological malignancies was 54 years (range, 40–70). Patients received a median of 4 weekly doses of LAB (range, 1–8), with 8 patients (53%) receiving at least 4 consecutive weekly doses. In terms of toxicity, 6 patients (40%) didn’t experience any sign of toxicity. One patient experienced a violent chest pain with transient extra-systoles, during the first infusion of LAB, and did not receive any subsequent infusions. Other mild and transient infusion-related reactions (fever, flush, tachycardia, orthostatic hypotension, pruritous, bone pain, abdominal pain) were observed in 5 patients, usually at time of first LAB infusion. Despite concomitant administration of cyclosporin A in all 15 patients, only 4 patients (27%) had to interrupt the course of prophylactic LAB (respectively after 3 (n=2), 4 and 7 infusions) because of renal toxicity (increase of serum creatinine ≥1.5 times from baseline values).

Conclusions. Although long term efficacy of such antifungal prophylactic strategy is yet to be established, the results of this feasibility study demonstrate that a weekly dose of 7.5 mg/Kg of LAB is relatively safe and well tolerated when given as prophylaxis in high-risk immuno-compromised patients receiving high dose CS for GVHD after RIC allo-SCT, despite concomitant administration of multiple nephrotoxic drugs.