galactomannan and Lymphoma

This study was conducted as a prospective, multicenter trial to evaluate the efficacy and safety of micafungin as an empirical therapy for suspected invasive fungal infections (IFIs), including febrile neutropenia (FN), and to evaluate the usefulness of β-D: -glucan (BG) and Aspergillus galactomannan (GM) antigen in patients with hematologic diseases. A total of 121 patients were enrolled and assessed for safety, and 119 were examined for clinical efficacy. The main underlying diseases were acute myeloid leukemia (38.0%), acute lymphoblastic leukemia (18.2%), and malignant lymphoma (18.2%). The median initial daily dose and duration of micafungin treatment were 150 mg/day and 13 days, respectively. The overall response rate for suspected IFIs (n = 119), based on four composite endpoints, including baseline IFI, breakthrough IFIs (proven and probable), survival, and premature discontinuation, was 79.0%. In addition, the response rate for FN (n = 81), based on these four endpoints as well as defervescence during neutropenia, was 39.5%. Breakthrough IFIs (proven, probable, and possible) occurred in five patients during micafungin treatment. All of these patients were positive for either BG or GM before the breakthrough IFIs. The incidence of adverse events (AEs) associated with micafungin was 10.7% and most were mild. The majority of AEs were liver dysfunction. These results indicate the effectiveness and safety of micafungin as an empirical therapy for suspected IFIs, including FN, and the usefulness of monitoring both BG and GM to detect breakthrough IFIs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Antigens, Bacterial; Aspergillosis; beta-Glucans; Candidiasis, Invasive; Chemical and Drug Induced Liver Injury; Early Diagnosis; Echinocandins; Female; Galactose; Hematologic Neoplasms; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Lymphoma; Male; Mannans; Micafungin; Middle Aged; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult

The performance of a sandwich enzyme-linked immunosorbent assay (ELISA) which detects Aspergillus galactomannan (GM) was evaluated in bronchoalveolar lavage (BAL) fluid samples from 19 patients who were treated for hematological malignancies and who were suspected of having invasive pulmonary aspergillosis (IPA). All patients had fever and pulmonary infiltrates on the chest roentgenogram on the day that the BAL fluid was obtained. The ELISA results were compared with the results of culture and Aspergillus genus-specific PCR analysis of BAL fluid samples. ELISA was also performed with serum samples. Aspergillus species were detected by PCR or ELISA with BAL fluid samples from five of seven patients who had radiological evidence of IPA. Serum ELISA results were positive for all patients with ELISA-positive BAL fluid, and for four patients the serum ELISA was positive before the BAL fluid was obtained. PCR and ELISA were positive for 2 and 1 of 10 BAL fluid samples, respectively, obtained from patients without radiological evidence of IPA, and 5 and 2 of 35 BAL fluid samples, respectively, obtained from nonneutropenic patients. This preliminary investigation suggests that GM may be detected by ELISA in BAL fluid samples from patients at risk of IPA, but that monitoring of serum GM levels may allow for the earlier diagnosis of IPA. However, further evaluation in prospective studies is required.

Topics: Adult; Aged; Antigens, Fungal; Aspergillosis; Aspergillus; Bronchoalveolar Lavage Fluid; Enzyme-Linked Immunosorbent Assay; Evaluation Studies as Topic; Female; Galactose; Hematologic Diseases; Humans; Leukemia; Lung Diseases, Fungal; Lymphoma; Male; Mannans; Middle Aged; Polymerase Chain Reaction; Sensitivity and Specificity