Itraconazole Prophylaxis for Invasive Aspergillosis in Severe Neutropenic Patients

Ha, Kyoung Won; Lee, Hong Ghi; Kim, Kihyun; Jung, Sook In; Kim, Jhingook; Kim, Seonwoo; Kim, Won Seog; Yoon, Sung Soo; Kang, Won Ki; Park, Keunchil; Park, Chan Hyung

Abstract

BACKGROUND
Invasive aspergillosis is an important cause of morbidity and mortality in neutropenic patients after chemotherapy in hematologic malignancies. HEPA filtration was known as an effective preventive measure for invasive aspergillosis, but the role of chemoprophylaxis has not been established yet. Itraconazole has been considered to be an effective antifungal agent for invasive aspergillosis. We evaluated the effect of itraconazole chemoprophylaxis in the prevention of invasive aspergillosis for neutropenic patients after chemotherapy in hematologic malignancies, who were treated in general ward without HEPA filtration.
METHODS
A total of 89 patients with hematologic malignancies were enrolled in the two groups between January, 1995 and December, 1997 at Samsung medical center. Itraconazole, 200 mg po twice daily, was given to the patients as their neutrophil count decreased below 1,000/microliter following chemotherapy, and continued until it recovered over 1,000/microliter. Incidence of invasive aspergillosis was prospectively compared between the itraconazole prophylaxis group and the control group.
RESULTS
Itraconazole prophyaxis was done in 34 patients on a total 59 episodes of severe neutropenia (absolute neutrophil count <500/microliter) after chemotherapy. Two out of 34 patients were histologically diagnosed as invasive aspergillosis. Control group included 55 patients with 103 episodes of severe neutropenia. Five out of 55 patients were diagnosed as invasive aspergillosis. No statistically significant differences were observed between two groups, because 2 of 59 (3.4%) and 5 of 103 (4.9%) were found to have invasive aspergillosis proven histologically (P=1.00).
CONCLUSION
Itraconazole chemoprophylaxis for invasive aspergillosis was not effective, and the prognosis was closely related to the recovery of neutrophils. But we cannot exclude thepossibility that the drug has been failed in achieving effective plasma concentration by oral administration, as reported in several studies. Randomized prospective study, including measurement of plasma drug concentration, is warranted to evaluate the efficacy of itraconazole for the prevention of invasive aspergillosis.