Immune Reconstruction Inflammatory Syndrome (IRIS) with Invasive Aspergillosis (IA) in Patients (pts) with Hematological Cancer (Hem-Ca): Clinical and Research Implications.

Background: Assessing IA outcome with conventional criteria is difficult particularly when clinical and radiological worsening coincides with neutrophil recovery. This worsening is assumed to be related to immune reconstitution (IRIS). Because it is not possible to distinguish between pts whose worsening is transient from those who have progressive IA, clinical and radiological deterioration usually prompts invasive diagnostic procedures and therapeutic modifications including investigational agents, surgery, others. Galactomannan (GM) is an Aspergillus-specific polysaccharide released during aspergillosis and detected by the serum GM test. This FDA-approved test is an accepted diagnostic marker for aspergillosis and preliminary data suggest a correlation between GM index (GMI) and outcome.

Purpose: using GMI, to distinguish response from progressive IA among patients with IRIS.

Patients and Methods: patients at risk for IA (11/03–2/06) underwent GMI screening during periods at risk. The clinical and laboratory findings of pts with ≥ 2 (+) GMI (optical density ≥ 0.5) were reviewed.

Results: 30 pts had GMI (+) aspergillosis of the respiratory tract [myeloma 92%; median age: 59 years (27–75); 15 males]. Invasive aspergillosis developed following stem cell transplantation [autologous (11), allogeneic (1)], or conventional chemotherapy (18). 12 of 25 (48%) neutropenic pts (<1000/ml) developed transient clinical and radiological worsening coinciding with neutrophil recovery, suggesting an IRIS. This deterioration coincided with rapidly declining GMI in 7 pts, all of whom survived with complete resolution of IA and without therapeutic modifications while the remaining 5 pts had persistently elevated GMI and rapidly died of IA.

Conclusion: These data establish the presence of IRIS among Hem-Ca pts with IA who suffer clinical and radiologic deterioration coinciding with neutrophil recovery. IRIS is common and occurs among both responders and non-responders. Declining GMI values implies IRIS with response and obviates the need for invasive procedures and / or therapy modification while persistent GMI elevation is indicative of IRIS with progressive infection. Serial GMI testing should be performed to guide management and evaluate pts prior to therapy with investigational antifungal agents.