Prolonged Granulocytopenia: The Major Risk Factor for Invasive Pulmonary Aspergillosis in Patients with Acute Leukemia

Abstract

A case-control study of patients with acute leukemia was done to identify significant risk factors for invasive pulmonary aspergillosis by reviewing the medical histories of 15 cases of pathologically proven invasive pulmonary aspergillosis and 45 controls. A history of lung or sinus disease, smoking, and multiple recurrences of leukemia did not increase the risk of invasive pulmonary aspergillosis. Cases and controls received similar chemotherapeutic regimens, and exposure to aminoglycosides, carbenicillin, trimethoprim-sulfamethoxazole, or corticosteroids was not significantly associated with development of invasive pulmonary aspergillosis. Among the factors tested, only granulocytopenia was associated with development of invasive pulmonary aspergillosis. Early in the course of granulocytopenia, patients developed signs of invasive pulmonary aspergillosis at a rate of approximately 1% per day. As the duration of granulocytopenia increased, the rate increased, approximating 4.3% per day between the 24th and 36th days. Of the 13 patients remaining granulocytopenic at 28 days, 7 had developed signs of invasive pulmonary aspergillosis. For patients with acute leukemia, granulocytopenia persisting longer than three weeks is the major risk factor for developing invasive pulmonary aspergillosis.

Macrophage Inflammatory Protein-1α Is a Critical Mediator of Host Defense Against Invasive Pulmonary Aspergillosis in Neutropenic Hosts

“…The commonest and best characterized risk factor for development of invasive aspergillosis is neutropenia (7,8). The role of neutrophils in the innate host defense against Aspergillus species has been well documented in both in vitro (9,10) and in vivo (11,12) experiments.…”

T Cell Vaccination in Mice with Invasive Pulmonary Aspergillosis

“…Resident alveolar macrophages ingest and kill resting conidia, largely through nonoxidative mechanisms, while neutrophils use oxygen-dependent mechanisms to attack hyphae germinating from conidia that escape macrophage surveillance (13,14). The effectiveness of this system is evident from the observation that challenge with even large numbers of conidia fails to cause disease in immunocompetent animals (17), and recognized major risk factors in humans are defects in phagocyte functions, such as those occurring in chronic granulomatous disease (18,19), cortisone-induced suppression of macrophage conidiocidal activity (20,21), and chemotherapy-induced neutropenia (22). Increased risk of a chronic form of IPA that is independent of neutropenia and corticosteroid therapy has been noticed in patients with HIV (8), who also showed a defective effector activity of neutrophils against A. fumigatus (23).…”

Invasive Pulmonary Aspergillosis in a Puerperant with Drug-induced Agranulocytosis.

“…Of these, IPA, an acute infection ofAspergillus species, occurs almost exclusively in immunocompromisedhosts. Although long-standing neutropenia is the major risk of IPA (1), there have been no previous case reports of IPA, which developed during drug-induced neutropenia in otherwise healthy patients. Here, we report a 30-year-old pregnant woman, whodeveloped drug-induced aganulocytosis and suffered from IPA soon after vaginal delivery.…”