Döring, M., Hartmann, U., Erbacher, A., Lang, P., Handgretinger, R., & Müller, I. (2012). Caspofungin as antifungal prophylaxis in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation: a retrospective analysis. BMC Infectious Diseases, 12, 151.

The primary objective was to evaluate the safety of caspofungin (CAS) in pediatric patients following allogeneic hematopoietic stem cell transplantation (HSCT) when compared with intravenous (IV) liposomal amphotericin B (L-AmB).  The secondary objectives evaluated the incidence of aspergillosis, candidiasis, and other fungal infections in pediatric patients following allogeneic HSCT.

This was a retrospective analysis of pediatric patients receiving either CAS or L-AmB after allogeneic HSCT between January 2006 and June 2010.  All patients received L-AmB (1 mg/kg/day) during conditioning from day –8 through day 0.  Patients who underwent transplantation between January 2006 and August 2008 were continued on L-AmB until oral antimycotic therapy was started prior to discharge (group 1).  All patients undergoing transplantation between September 2008 and June 2010 were switched to CAS starting on day 1 until oral antimycotic therapy was started prior to discharge (group 2).  The observation period was defined as the time from the start of IV antimycotic prophylaxis until three weeks after switching to oral antimycotic prophylaxis three to four days before inpatient discharge.  Patients were observed for tolerability, safety, and efficacy of caspofungin, and infection rates were compared between the two groups.

• One hundred twenty patients were included.
• Patients were younger than 18 years.  Twenty patients were younger than 6 years in the L-AmB arm and 17 were in the CAS arm; 24 patients were aged 6 to 11 years in L-AmB arm and 20 were in the CAS arm; and 16 patients were aged 12 to 18 years in the L-AmB arm and 23 were in the CAS arm.
• In the L-AmB arm, 55% of patients were male and 45% were female.  In the CAS arm, 63.3% of patients were male and 36.7% were female.
• Key disease characteristics were patients with hematologic malignancies.  Nonmalignant hematologic disorders and inborn errors of metabolism undergoing allogeneic HSCT were evaluated. The L-AmB arm included patients with acute lymphoblastic leukemia (ALL) (30%), acute myeloid leukemia (AML) (11.7%), juvenile myelomonocytic leukemia (JMML) (5%), chronic myelogenous leukemia (CML) (5%), myelodysplastic syndromes (MDS) (10%), non-Hodgkin Lymphoma (NHL) (1.7%), solid tumors (15%), aplastic anemia (1.7%), neurometabolic diseases (8.3%), immunodeficiency (6.7%), Chediak-Higashi syndrome (3.3%), and Morbus Kostmann (1.7%).  The CAS arm included patients with ALL (28.3%), AML (1.7%), JMML (3.3%), MDS (8.3%), NHL (5%), solid tumors (16.7%), aplastic anemia (16.7%), neurometabolic diseases (8.3%), and immunodeficiency (11.7%).
• In the L-AmB arm, 53.4% of patients had some degree of graft-versus-host disease; in the CAS arm, 61.9% of patients had any degree of graft-versus-host disease.

• Single site 
• Inpatient 
• University Children’s Hospital Tubingen, Germany

• Patients were undergoing the active antitumor treatment phase of care.
• The study has clinical applicability for pediatrics.

This was a single-center, retrospective study.

Biochemical laboratory results were measured.

Leukopenia was observed for a median duration of 12 days in both groups.  Median duration of therapy was 23 days (range 9–72) in group 1 (L-AmB) and 24 days (range 14–49) in group 2 (CAS).  There was no incidence of proven aspergillosis or another invasive fungal infection in either group.  No proven fungal breakthrough infections were observed in either group three weeks after the conclusion of IV fungal therapy.  No patient died of an invasive fungal infection. Clinical side effects related to treatment were observed in 8.3% of patients in group 1 and 3.3% in group 2, with four patients in the L-AmB arm being switched to CAS due to side effects.  There was a statistically significant but transient increase in alanine aminotransferase (ALT)/aspartate aminotransferase (AST) in both groups, and hypokalemia occurred significantly (p = 0.006) in the L-AmB arm (group 1).

This study retrospectively showed that the efficacy of the two antifungal agents used for prophylaxis was good with no proven invasive fungal infection noted in either group.  This could be an option to limit the side effects and potential nephrotoxicity noted in L-AmB administration.  Larger, prospective studies are needed for true recommendations.

• Risk of bias (no control group, no blinding, no random assignment, no appropriate attentional control condition)
• Findings not generalizable*

* Findings may not be generalizable to adult patients, but they could be generally applied to pediatric patients undergoing allogeneic HSCT, which is a small group.

Nursing is imperative in the monitoring and administration of medications in this setting.  The need for monitoring, especially for infusion reactions, hypokalemia, and nephrotoxicity, is higher in those receiving L-AmB.  The use of CAS may reduce this need, but nurses must still be vigilant to identify fever or other symptoms in these patients.