Performance of IFIGC/MSG/EORTC Criteria for the Diagnosis of Invasive Pulmonary Aspergillosis in the Clinical Management of Unselected Patients with Acute Leukemia.
Authors: Borlenghi Erika , Capucci Maria Adele , Cattaneo Chiara , Petrella Nicoletta , Signorini Liana , Franco Fabio , Rossi Giuseppe 
Published: October 2019

Abstract
Invasive pulmonary aspergillosis (IPA) is a severe complication in patients (pts) treated for acute leukemia. Since its diagnosis is still difficult, sets of non-invasive diagnostic criteria were recently proposed by IFIGC/MSG/EORTC for study purposes. The performance of those criteria in the clinical management of unselected leukemic pts is still unknown. We have therefore applied IFIGC/MSG/EORTC criteria to the diagnosis of pulmonary infiltrates occurred in 83 consecutive pts, aged <65, with newly diagnosed acute leukemia (19 APL, 38 AML, 26 ALL) treated at a single Institution between 1/2000 and 12/2003. The frequency of the different categories of IPA as diagnosis of pulmonary infiltrates and the relative contribution of the specific sets of diagnostic criteria were analysed. Forty-one pulmonary infiltrates developed in 30/83 pts (36.1%), during 364 chemotherapy cycles. IPA was diagnosed in 22 pts (26.5%). “Proven” IPA occurred in 1 (1.2%), “probable” IPA in 7 (8.4%) and “possible” IPA in 14 pts (16.8%). IPA was significantly more frequent in AML (36,8%), than in APL (15,7%) or ALL (15,3%) (P=0.041), and during the first induction (21/83; 25.3%) than during subsequent cycles (20/281; 7.1%) (P< 0.001). Considering the episodes of pulmonary infiltrate, IPA criteria were met in 27/41 (65,8%) [1 “proven”, 7 “probable” (17%) and 19 “possible” (46,3%)]. Specifically, “host criteria” were met in 41/41 (100%), “microbiological criteria” in 8/41 (17%), and “clinical criteria” in 27/41 (65,8%). The presence of one “major clinical” criterion, i.e. a typical radiological image on chest Xray or CT, was significantly associated with the positivity of a “microbiological” criterion, hence with a diagnosis of “probable” IPA (P=0,012). On the other hand, since “host” criteria were not discriminant, being positive in 100% of cases, the presence of two aspecific “minor clinical” criteria (dyspnea, cough, pleural rub, chest pain, hemophtysis) was the sole responsible for the classification of any non-typical pulmonary infiltrate either as “possible” IPA (17/19 cases; 84.2 %) or as “no IPA”. The bacterial origin of the pulmonary infiltrate was documented on follow-up in 5/19 “possible” IPA, which responded to specific antibacterial treatment. All patients had received antifungal prophylaxis, in 88% with oral itraconazole. A clinical response to ampho/voriconazole was obtained in 6/8 (71,4%) “proven/probable” and 17/19 (89,4%) “possible” IPA. Four of 22 pts with IPA (2 “probable” and 2 “possible”) died early during aplasia (multiorgan failure (MOF) 3, cerebral hemorrhage 1) compared to 2/8 pts without IPA (MOF 1, leukemia 1). In conclusion, according to IFIGC/MSG/EORTC criteria, IPA was diagnosed in 26.5% of pts with acute leukemia and in 65,8% of pulmonary infiltrates. AML and the first induction cycle were significant risk factors. “Proven” IPA was rare. “Probable” IPA was more frequent (8,4% of pts), its diagnosis being strongly supported by the association of a “major” clinical criterion with one microbiological criterion. “Possible IPA” likely represents an overestimation (43,9% of pulmonary infiltrates) since its diagnosis derived in most cases from the combined presence of a “host” criterion with two “minor” aspecific clinical criteria. These data allow a critical analysis of IFIGC/MSG/EORTC criteria in the setting of acute leukemia.