Safety of a Weekly Administration of 10 mg/kg of Liposomal Amphotericin B for Antifungal Prophylaxis in Allogeneic Stem-Cell Transplant and Acute Leukemia Patients.

Background

Optimal antifungal prophylaxis approach for patients undergoing chemotherapy, acute leukaemia (AL) or allogeneic stem cell transplant (ASCT) for haematological malignancies has yet to be identified in this high risk setting.

Patient and Methods

An open-label, pilot multicentre study - initiated at Henri Mondor and St-Louis Hospitals (10 patients), Paoli-Calmettes Institute being secondary involved (13 patients) - was conducted between February 2004 and June 2005 in adult patients receiving induction or consolidation chemotherapy for AL or a myeloablative conditioning regimen for ASCT. Patients were either treated for 4 weeks (AL) from the beginning of chemotherapy or 8 weeks (ASCT) from transplant. Treatment consisted of a 2 hour weekly infusion of 10mg/kg liposomal amphotericin B (LAB). Premedication was not allowed prior to day 1 study drug infusion. The primary endpoint was the incidence of reported adverse events occurring during the course of prophylaxis treatment.

Results

Twenty three patients (14 males and 9 females), mean age 44 years (range: 20 to 79) were treated in this interim analysis (8 ASCT and 15 AL). Safety was monitored with particular attention to infusion-related reactions (IRRs) and nephrotoxicity. In a total of 60 infusions, 5 IRRs (8.3%) occurred (flush, shock, thoracic pain, bone pain and dyspnoea). These were exclusively observed on day one in 5 patients (21%). Seven patients (30%) reached serum creatinine (SCr) ≥1.5 times their baseline values. In the AL group, no patient discontinued LAB or required dose reduction during the study. In the ASCT group, 4 patients discontinued after the first infusion, 3 for IRRs and one for SCr increase related to the study drug and other factors, including reactions to concomitant drugs. One additional ASCT patient had discontinued study drug following the third infusion for SCr increase. Mean duration of prophylaxis was 18 days (range: 10–28) in the AL patients and 14 days (range: 6–31) in the ASCT patients.

Conclusion

A weekly dose of 10 mg/kg appears to be very well tolerated during induction or consolidation therapy for AL. In the ASCT setting where multiple drugs are concomitantly administered, appropriate timing for the initiation of high dose LAB prophylaxis is yet to be determined in order to optimise the safety profile of this regimen.