Breakthrough invasive aspergillosis and diagnostic accuracy of serum galactomannan enzyme immune assay during acute myeloid leukemia induction chemotherapy with posaconazole prophylaxis

Abstract

Posaconazole prophylaxis has demonstrated efficacy in the prevention of invasive aspergillosis during prolonged neutropenia following acute myeloid leukemia induction chemotherapy. Antifungal treatment decreases serum galactomannan enzyme immunoassay diagnostic accuracy that could delay the diagnosis and treatment.We retrospectively studied patients with acute myeloid leukemia who underwent intensive chemotherapy and antifungal prophylaxis by posaconazole oral suspension. Clinical, radiological, microbiological features and treatment response of patients with invasive aspergillosis that occurred despite posaconazole prophylaxis were analyzed. Diagnostic accuracy of serum galactomannan assay according to posaconazole plasma concentrations has been performed.A total of 288 patients with acute myeloid leukemia, treated by induction chemotherapy, who received posaconazole prophylaxis for more than five days were included in the present study. The incidence of invasive aspergillosis was 8% with 12 (4.2%), 8 (2.8%) and 3 (1%), possible, probable and proven invasive aspergillosis, respectively. Posaconazole plasma concentration was available for 258 patients. Median duration of posaconazole treatment was 17 days, and median posaconazole plasma concentration was 0.5 mg/L. None of patients with invasive aspergillosis and posaconazole concentration ≥ 0.5 mg/L had a serum galactomannan positive test. Sensitivity of serum galactomannan assay to detect probable and proven invasive aspergillosis was 81.8%. Decreasing the cut-off value for serum galactomannan optical density index from 0.5 to 0.3 increased sensitivity to 90.9%.In a homogenous cohort of acute myeloid leukemia patients during induction chemotherapy, increasing the posaconazole concentration decreases the sensitivity of serum galactomannan assay.

Breakthrough Invasive Fungal Infections in Allogeneic Hematopoietic Stem Cell Transplantation

“…The role of GM monitoring in the diagnostic work-up of patients receiving MAP is controversial, due to lower sensitivity and specificity [ 19 ]. However, these findings were mainly confirmed by studies with Posaconazole as MAP, rather than all studies [ 20 ]. Therefore, GM monitoring is still routinely performed in many centers when a b-IFI is clinically suspected in the setting of high-risk hematological patients [ 7 , 21 ].…”

Diagnosis of Breakthrough Fungal Infections in the Clinical Mycology Laboratory: An ECMM Consensus Statement

“…Specificity is also a concern, especially with non-sterile samples, because highly sensitive molecular techniques can also reflect the presence of commensal yeasts. (59). Slightly reduced sensitivities in the presence of mold-active antifungals has also been described for the BAL GM: at a cut-off of 0.5 optical density index (ODI), Eigl and colleagues showed a 71% sensitivity for probable/proven IA in those on antifungals versus 95% in those without antifungals (60,61).…”

Central Nervous System Mold Infections in Children with Hematological Malignancies: Advances in Diagnosis and Treatment

“…Circulating GM may become positive several days prior to the clinical manifestation of invasive aspergillosis [42], but circulation of GM in serum is transient, and therefore, screening testing should be done at least twice a week [36]. False-positivity has been described by the administration of various antibiotic compounds or the transfusion of antiglobulin or blood, whereas mold-active antifungal prophylaxis significantly decreases the sensitivity of the assay [43,44]. Notably, cross-reactivity has been observed with Penicillium, Histoplasma or Fusarium species [45].…”