Kim, Y. J., Sung, K. W., Hwang, H. S., Jung, S. H., Kim, J. Y., Cho, E. J., . . . Koo, H. H. (2011). Efficacy of itraconazole prophylaxis for autologous stem cell transplantation in children with high-risk solid tumors: a prospective double-blind randomized study. Yonsei Medical Journal, 52, 293–300.

To evaluate the effectiveness of prophylactic itraconazole in preventing fungal infections in pediatric autologous hematopoietic stem cell transplant (HSCT) recipients.

Patients with high-risk solid tumors undergoing autologous HSCT were divided into prophylaxis and empirical treatment groups to evaluate the effectiveness of itraconazole prophylaxis in pediatric autologous HSCT.  High-risk solid tumors included high-risk neuroblastoma, high-risk embryonal brain tumor, bilateral advanced retinoblastoma, and relapsed solid tumors. Patients were then randomized to prophylaxis or empirical treatment groups.  In the prophylactic group, itraconazole was given intravenously at 2.5 mg/kg/dose twice daily for the first two days followed by 2.5 mg/kg/dose once daily for the duration of treatment after the absolute neutrophil count (ANC) fell below 0.5x10⁹/L, even in the absence of fever.  In the empirical treatment group, a placebo was given once the ANC fell below 0.5x10⁹/L after the initiation of high-dose chemotherapy, and itraconazole was started only when a fever persisted for more than three days or if fever recurred despite the use of first-line antibiotics (in this case, cefepime) for more than three days. All antibiotics, including itraconazole, were discontinued after three consecutive days of no significant fever (<37.5°C), no evidence of documented or clinically suspected infection, and an ANC greater than 0.5x10⁹/L.  For microbiologically documented infections, the antibiotic regimen was altered as needed.

• Fifty-five patients who underwent 90 autologous HSCTs were included.  
• Median age was 49 months (range 15–300) in the prophylactic group and 46 months (range 17–302) in the empirical group.
• The numbers and percentages of males and females were not reported.
• Key disease characteristics were neuroblastoma (38.1% in the prophylactic group, 41.9% in the empirical group), brain tumor (40.5% in the prophylactic group, 44.2% in the empirical group), retinoblastoma (9.5% in the prophylactic group, 9.3% in the empirical group), Wilms' tumor (4.8% in the prophylactic group, 4.7% in the empirical group), osteoscarcoma (4.8% in the prophylactic group, 0 patients in the empirical group), and primitive neuroectodermal tumor (1 patient in the prophylactic group, 0 patients in the empirical group).  Patients were newly diagnosed (83.3% in the prophylactic group, 83.7% in the empirical group) or had relapsed (16.7% in the prophylactic group, 16.3% in the empirical group).
• Patients were either receiving their first HSCT (47.6% in the prophylactic group, 53.5% in the empirical group) or their second HSCT (52.4% in the prophylactic group, 46.5% in the empirical group). Time to ANC greater than 0.5x10⁹/L was 10 days (range 8–15) in the prophylactic group and 9 days (range 7–16) in the empirical group; duration of ANC of less than 0.5x10⁹/L was 11 days (range 6–22) in the prophylactic group and 10 days (range 5–18) in the empirical group.
   

• Single site  
• Inpatient
• Pediatric Stem Cell Transplantation Unit of Samsung Medical Center

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

This was a prospective double-blind, randomized study.

• Total duration of fever    
• Duration of antibiotic treatment
   

No cases of proven, probable, or possible invasive fungal infection occurred in either group.  The duration of fever higher than 38ºC was significantly shorter in the prophylaxis group than in the empirical group.  The number of patients who had fever for more than seven days, which was the duration of antibiotic use, and the number of patients who needed additional second-line antibiotic treatment, were lower in the prophylactic group than in the empirical group.  There was no difference in the development of serious adverse events between the prophylaxis group and the empirical treatment group.  The expected benefit of prophylaxis in patients with severe mucositis did not seem to be relevant because there was a reduced duration of fever regardless of the severity of mucositis.

Although there were no infections in the prophylactic group, this was not different than the results in the empirical group.  There was no statistically significant finding to come from this study.  There were some promising findings, such as decreased need for second-line antibiotics and decreased duration of fever, but a larger study would be necessary to prove that these are relevant findings because the power was not high enough in this study.  This was a limited population, and the findings may not be generalizable to adult patients undergoing HSCT.

•  Small sample (<100)
•  Drug levels of itraconazole were not measured.
   

This article educated about fungal infections and the need for antibiotics, as well as neutropenia and the expected adverse effects of transplant.  There are no specific nursing implications for this study because there were no significant findings.