Efficacy and Safety of Low-Dose Liposomal Amphotericin B in Adult Patients Undergoing Unrelated Cord Blood Transplantation

Abstract

Liposomal amphotericin B (L-AMB) is widely used for empirical or preemptive therapy and treatment of invasive fungal infections after cord blood transplantation (CBT). We retrospectively examined the efficacy and safety of low-dose L-AMB in 48 adult patients who underwent CBT between 2006 and 2017 in our institute. Within the entire cohort, 42 patients (88%) received L-AMB as empirical or preemptive therapy. The median daily dose of L-AMB and the median cumulative dose of L-AMB were 1.20 mg/kg/day (range, 0.62 to 2.60 mg/kg/day) and 30.6 mg/kg (range, 0.7 to 241.5 mg/kg), respectively. The median duration of L-AMB administration was 21.5 days (range, 1 to 313 days). A documented breakthrough fungal infection occurred in 1 patient during L-AMB treatment, and 43 patients (90%) survived for at least 7 days after the end of L-AMB treatment. Grade 3 or higher hypokalemia and hepatotoxicity were frequently observed during L-AMB treatment. However, no patient developed an increase in serum creatinine levels of grade 3 or higher. In univariate analyses using a logistic regression model, a duration of L-AMB treatment of more than 21 days and a cumulative dose of L-AMB of more than 30 mg/kg were significantly associated with nephrotoxicity and grade 3 hypokalemia. These data suggest that low-dose L-AMB may be safe and effective in adult patients undergoing CBT.

Keywords: allogeneic hematopoietic cell transplantation; cord blood transplantation; hepatotoxicity; invasive fungal infection; liposomal amphotericin B; nephrotoxicity.

FIG 1

Kinetics of hepatic and renal function parameters and electrolyte levels at baseline, the maximum or minimum values during L-AMB treatment, and the values at the end of therapy. The line inside the box, the lower and upper box ends, and the lower and upper whiskers represent the median value, the 25th and 75th percentiles, and the 10th and 90th percentiles of each value, respectively. The statistical differences between two groups (baseline values, maximum or minimum values during L-AMB, and values at the end of therapy) were analyzed with Kruskal-Wallis and Steel-Dwass tests. *, P < 0.05; **, P < 0.01; ***, P < 0.001; NS, not significant; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; T-bil, total bilirubin; BUN, blood urea nitrogen; Cre, creatinine; K, potassium; Mg, magnesium.