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Jae-Cheol Kwon, Si-Hyun Kim, Su-Mi Choi, Jae Ki Choi, Dong-Gun Lee
, Sun Hee Park, Jung-Hyun Choi, Jin-Hong Yoo, Wan-Shik Shin
, Sun Hee Park, Jung-Hyun Choi, Jin-Hong Yoo, Wan-Shik Shin
Abstract
Background
Invasive aspergillosis (IA) is associated with significant morbidity and mortality in patients with hematologic malignancies. We investigated the efficacy and safety of voriconazole (VCZ) when used as salvage therapy for IA in Korean adults with hematologic malignancies who had not responded to prior antifungal therapy.
Materials and Methods
We retrospectively reviewed data, collected from January 2007 to October 2008, from patients with proven or probable cases of IA. All were probable IA cases, except for one proven case. All cases were refractory or intolerant to antifungal therapy prior to administration of VCZ. Efficacy and safety were assessed in patients treated with VCZ for more than 3 days and for more than one dose, respectively. A favorable response [complete (CR) or partial (PR)] was defined by significant improvement of all clinical symptoms, signs, and radiologic abnormalities.
Results
Fifty patients who met the inclusion criteria were enrolled. There were 27 male and 23 female patients with mean age of 44.4 years (range, 15-65 years). Underlying diseases were acute leukemia (35 cases), chronic myelogenous leukemia (4 cases), myelodysplastic syndrome (3 cases), lymphoma (3 cases) and other hematologic diseases (5 cases). Twenty-two patients had received chemotherapy and 13 patients had undergone hematopoietic stem cell transplantation. The lung was the main infection site (94%) followed by the sinus (6%). Amphotericin B deoxycholate alone was the most frequent previous antifungal therapy. The mean duration of antifungal therapy prior to VCZ therapy was 13.9±8.8 days (2-44 days). The median duration of VCZ therapy was 19 days (interquartile range, 49 days). Sixteen patients (32.0%) showed favorable responses (CR:PR=8:8) at the end of VCZ therapy. The numbers of patients with stable disease, progression and death were, 6 (12%), 6 (12%) and 22 (44%) respectively. Most of those with unfavorable responses had relapsed underlying malignancies or refractory graft versus host diseases. Twelve patients developed drug-related adverse events but only one patient stopped VCZ treatment prematurely.
References
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Figure 1.
Kaplan-Meier probability of overall survival rate after initiation of VCZ therapy according to underlying disease status. Group A includes chemotherapy, HSCT and post-HSCT groups collectively. Group B is conservative care group. One patient in group B was missing 31 days after enrollment. The P value was calculated by the Log-rank test.
Table 1.
Baseline Demographic and Clinical Characteristics of Patients
| Characteristics | No. (%) of patients (n=50) |
|---|---|
| Sex | |
| Male | 27 (54.0) |
| Female | 23 (46.0) |
| Mean age±SD [range], years | 44.4±12.6 [15-65] |
| Underlying disease | |
| AML | 27 (54.0) |
| ALL | 8 (16.0) |
| CML | 4 (8.0) |
| MDS | 3 (6.0) |
| Lymphoma | 3 (6.0) |
| Others* | 5 (10.0) |
| Treatment group | |
| Chemotherapy group | 22 (44.0) |
| HSCT and Post-HSCT group | 13 (26.0) |
| Conservative care | 15 (30.0) |
| Classification of IA | |
| Proven | 1 (2.0) |
| Probable | 49 (98.0) |
| Site of IA | |
| Lung | 47 (94.0) |
| Sinus | 3 (6.0) |
| Response to initial antifungal therapy | |
| Refractoriness | 48 (96.0) |
| Intolerance | 2 (4.0) |
| Neutropenia at enrollment | |
| Neutropenic | 23 (46.0) |
| Non-neutropenic | 27 (54.0) |
| Duration of previous antifungal theapy | |
| Mean±SD (days) | 13.9±8.8 |
| >7 days | 35 (70.0) |
| >30 days | 3 (6.0) |
| Duration of voriconazole therapy | |
| Median (days) | 19 |
| IQR (days) | 49 |
| >90 days (%) | 10 (20.0) |
Table 2.
Overall Efficacy of Voriconazole Therapy
Table 3.
Distribution of Patients with a Favorable Response to Voriconazole Therapy at the End of Therapy
| Factors | No. of patients with favorable response/total No. of assessable patients (%) |
|---|---|
| Underlying disease | |
| AML | 10/27 (37.0) |
| ALL | 3/8 (37.5) |
| CML | 1/4 (25.0) |
| MDS | 2/3 (66.7) |
| Lymphoma | 0/3 (0.0) |
| Others* | 0/5 (0.0) |
| Treatment group | |
| Chemotherapy group | 9/22 (40.9) |
| HSCT & post-HSCT group | 5/13 (38.5) |
| Conservative care | 2/15 (13.3) |
| Classification of IA | |
| Proven | 0/1 (0.0) |
| Probable | 16/49 (32.7) |
| Site of IA | |
| Lung | 16/47 (34.0) |
| Sinus | 0/3 (0.0) |
| Response to initial antifungal therapy | |
| Refractoriness | 15/48 (31.3) |
| Intolerance | 1/2 (50.0) |
| Neutropenia at enrollment | |
| Neutropenic | 6/23 (26.1) |
| Non-neutropenic | 10/27 (37.0) |
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