Abstract
BackgroundPediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) often receive intravenous liposomal amphotericin B (L-AmB) as antifungal prophylaxis. There are no guidelines for antifungal prophylaxis in children in this situation. Caspofungin (CAS), a broad-spectrum echinocandin, could be an effective alternative with lower nephrotoxicity than L-AmB.MethodsWe retrospectively analyzed the safety, feasibility, and efficacy of CAS in our center, and compared the results with L-AmB as antifungal monoprophylaxis in pediatric patients undergoing HSCT. 60 pediatric patients received L-AmB (1 or 3 mg/kg bw/day) and another 60 patients received CAS (50 mg/m2/day) as antifungal monoprophylaxis starting on day one after HSCT. The median ages of patients receiving L-AmB and CAS were 7.5 years and 9.5 years, respectively.ResultsNo proven breakthrough fungal infection occurred in either group during the median treatment period of 23 days in the L-AmB group and 24 days in the CAS group. One patient receiving CAS developed probable invasive aspergillosis. During L-AmB treatment, potassium levels significantly decreased below normal values. Patients treated with L-AmB had more drug-related side effects and an increased need for oral supplementation with potassium, sodium bicarbonate and calcium upon discharge as compared with the CAS group. CAS was well-tolerated and safe in this cohort of immunocompromised pediatric patients, who underwent high-dose chemotherapy and HSCT.ConclusionProphylactic CAS and L-AmB showed similar efficacy in this biggest cohort of pediatric patients after allogeneic HSCT reported, so far. A prospective randomized trial in children is warranted to allow for standardized guidelines.
Highlights
Pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) often receive intravenous liposomal amphotericin B (L-AmB) as antifungal prophylaxis
All pediatric patients included in the survey, a total of 60 patients in the first group and an additional 60 patients in the second group, received antimycotic prophylaxis with L-AmB (1 mg/kg/day) from the beginning of conditioning until day 0
In 34 (56.7%) of the 60 pediatric patients in the L-AmB group, the antimycotic prophylaxis with L-AmB was adjusted after HSCT to 3 mg/kg/day from the initial dosage of 1 mg/kg/day due to fever greater than or equal to 38.5°C
Summary
Pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) often receive intravenous liposomal amphotericin B (L-AmB) as antifungal prophylaxis. Caspofungin (CAS), a broad-spectrum echinocandin, could be an effective alternative with lower nephrotoxicity than L-AmB. Pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) are at high risk of acquiring severe invasive opportunistic fungal infections. Risk factors include extensive immunosuppression, cytopenia, T-cell depletion of the graft, graft-versus-host disease (GvHD), underlying disease and viral or bacterial infections [1,2]. Nephrotoxicity or infusion-related side effects have been reported in some studies in adolescents and adults [13,14,15]. Multicenter trial with 343 neutropenic pediatric and adult patients empirically treated with L-AmB, side effects included creatinine increase (19% of cases), fever (17%), and rigor (18%) [16]. Maculopapular rash, itching, and hyperphosphatemia were reported in case reports of pediatric patients when L-AmB was used [17,18]
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