Outcome of Invasive Aspergillosis (IA) in 30 Patients with Hematological Cancer (Hem-Ca): Immunity Is (Almost) Everything.

Abstract

Background: Among IA pts receiving antifungal therapy, a strong relationship exists between outcome of IA and resolution of immunosuppression. Determining the respective contributions of immune reconstitution and antifungal therapy to response has not been attempted. Yet, treatment strategies for IA have focused almost exclusively on antifungal agents to the detriment of immune therapies. 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 describe the contribution of immune recovery to outcome of IA in pts with hematological cancer (Hem-Ca).Patients and Methods: From 11/03–2/06, pts at risk for IA underwent GMI screening during periods at risk. The clinical and radiological findings of pts with ≥ 2 positive (+) 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]. Aspergillosis developed following stem cell transplant (SCT) [autologous (11), allogeneic (1)], or conventional chemotherapy (18). 25 pts were neutropenic (<1000/ml). The critical role of immune reconstitution was evident in 15/30 pts (50%). 7 of 25 (28%) neutropenic pts developed transient clinical and radiological worsening coinciding with immune recovery and rapid decline in GMI. All 7 responded without treatment modifications, suggesting an immune reconstitution inflammatory syndrome (IRIS). 6 pts had spontaneous clinical response with GMI normalization before commencing antifungal therapy (4 after neutrophil recovery, and 2 non-neutropenic pts after tapering immunosuppressants). 2 pts with IA refractory to prolonged and maximal antifungal therapy rapidly responded to interferon γ (1) and leukocyte transfusions (1) with GMI normalization within 48 h and subsequent clinical response.Overall, all 3 pts who remained neutropenic died compared to 2 of 22 pts whose myelosuppression resolved and 1/5 non-neutropenic pts (p=0.005).Conclusion: In addition to the strong association between neutrophil recovery and IA response, the critical role of immunity in IA is supported by common development of IRIS, spontaneous resolution of IA and response to immunomodulatory therapies. Daily GMI testing should be performed to accurately assess aspergillosis response. Declining GMI index obviates the need for invasive procedures and / or therapy modification. Immune therapies should be explored in IA.