Prophylactic Application of Nebulized Liposomal Amphotericin B in Hematologic Patients with Neutropenia

Abstract

Background: Pulmonary invasive fungal infections (IFI) are well-recognized complications with high morbiditiy and mortality in patients with hematologic malignancies. Patients and Methods: Aerosolized liposomal amphotericin B (lipAmB) was evaluated as an antifungal prophylaxis in patients with an expected neutropenia of more than 10 days due to intensive chemotherapy or stem cell transplantation, in a prospective phase II trial. Results: 98 treatment episodes were included in the study and compared to 105 historical control patients. Inhalation was performed between 0 and 103 days. No severe side effects of therapy occurred. 40 patients considered inhalations as unpleasant, 2 as very unpleasant, mostly due to bad taste or cough. Few cases of definite or probable IFI were recorded, whereas a large number of patients were treated with systemic antifungal therapy for pneumonia or fever of unknown origin without a significant difference between study patients and controls. In a predefined subgroup analysis of 48 patients with newly diagnosed acute myeloid leukemia (AML), significantly more patients survived for 1 year in the AmB prophylaxis than in the control group (80% vs. 54%, p < 0.01). Conclusions: Inhalations of lipAmB are feasible and safe. Results in the subgroup of patients with AML together with data from other trials suggest further evaluation of effectiveness.

Inhaled Amphotericin B as Aspergillosis Prophylaxis in Hematologic Disease: An Update

“…14,16 Two historically controlled trials failed to report a statistical analysis on IA incidence limiting their use in this analysis. 11,15 Overall IPA incidence was highest in Rijnders et al 14 (4% InLipAmB vs 14% control) and Chong et al 16 (9.5% InLipAmB vs 23.4% control), both were conducted in the same center in the Netherlands. The higher IPA rate may be attributed to the more rigorous surveillance and diagnostic testing used compared with other studies, ie, EORTC-MSG criteria in addition to highresolution computed tomography for abnormal chest X-ray or day 5 of unexplained fever.…”

“…[11][12][13][14][15][16] Two trials were prospective, randomized, and controlled, 12,14 whereas 4 trials employed historical controls. 11,13,15,16 Four studies included a mixture of SCT recipients and/or hematologic malignancy patients, 11,12,14,15 whereas the single studies included allogeneic SCT recipients receiving high-dose steroids for GvHD, 13 or patients with hematologic malignancies without SCT. 16 The primary endpoint for all of the trials was proven or probable IPA or IA incidence.…”

“…13,14,16 All trials required histologic evidence for proven infection. [11][12][13][14][15][16] A total of 3 trials, 1 InAmB D 13 and 2 InLipAmB, identified statistical significance in favor of InAmB prophylaxis. 14,16 Two historically controlled trials failed to report a statistical analysis on IA incidence limiting their use in this analysis.…”

“…Hullard-Pulstinger et al 15 conducted a prospective, nonrandomized, open-label, phase II trial to determine efficacy and safety of InLipAmB (93 patients) in the setting of persistent neutropenia vs untreated historical controls (105 patients).…”

“…Patients adhering to the protocol received a mean of 43.6 days of treatment, whereas those discontinuing early received a mean of 26.7 days. 15 Strengths include the use of a control group and prospective safety evaluation. Limitations include the open-label study design, no IPA statistical analysis reported, and confounding factors such as medical advances that may have occurred when using historical controls.…”